Original Article
Is familial screening useful in selective immunoglobulin A deficiency?
¿Es útil el cribado familiar en el déficit selectivo de inmunoglobulina A?
P. Soler-Palacína,
, E. Cobos-Carrascosaa, A. Martín-Naldaa, F. Caracseghia, M. Hernándezb, C. Figueras-Nadala
Corresponding author
a Unidad de Patología Infecciosa e Inmunodeficiencias Pediátricas, Hospital Universitari Vall d’Hebron, Institut de Recerca Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
b Servicio de Inmunología, Hospital Universitari Vall d’Hebron, Institut de Recerca Vall d’Hebron Universitat Autònoma de Barcelona, Barcelona, Spain
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CI: caso índice; DSIgA: déficit selectivo de IgA; FPG: familiares de primer grado; CE: caso esporádico; CF: caso familiar; FPG-E: familiares de primer grado enfermos; FPG-S: familiares de primer grado sanos.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "P. Soler-Palacín, E. Cobos-Carrascosa, A. Martín-Nalda, F. Caracseghi, M. Hernández, C. Figueras-Nadal" "autores" => array:6 [ 0 => array:2 [ "nombre" => "P." "apellidos" => "Soler-Palacín" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Cobos-Carrascosa" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Martín-Nalda" ] 3 => array:2 [ "nombre" => "F." "apellidos" => "Caracseghi" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Hernández" ] 5 => array:2 [ "nombre" => "C." 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"apellidos" => "Figueras-Nadal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad de Patología Infecciosa e Inmunodeficiencias Pediátricas, Hospital Universitari Vall d’Hebron, Institut de Recerca Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Inmunología, Hospital Universitari Vall d’Hebron, Institut de Recerca Vall d’Hebron Universitat Autònoma de Barcelona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "¿Es útil el cribado familiar en el déficit selectivo de inmunoglobulina A?" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2076 "Ancho" => 2809 "Tamanyo" => 217626 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Description of the studied sample. IC: index case; SIgAD: selective IgA deficiency; FDR: first-degree relatives; SC: sporadic case; FC: familial case; FDR-A: affected first-degree relatives; FDR-H: healthy first-degree relatives.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Selective IgA deficit (SIgAD) belongs to the group of primary immunodeficiencies characterised by a deficit in the production of antibodies. Although SIgAD is the most frequent primary immunodeficiency (PID), its prevalence may vary from 1/163 to 1/18,500 cases, based on the studied population and the definition of SIgAD.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1,2</span></a> These variations support a genetic predisposition, and new cases can appear sporadically or be transmitted in a dominant autosomal or recessive manner, or through polygenic inheritance. Thus, a 30% probability of SIgAD has been estimated if there is an affected relative,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> but no specific genetic defect has been identified, nor has a clear Mendelian inheritance pattern been proven, and expression and penetrance differences persist.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,4,5</span></a> Several genes potentially implicated in its pathogenesis have been identified, suggesting that SIgAD is probably a heterogeneous group of diseases and/or genetic anomalies similar to common variable immunodeficiency (CVID), notably transmembrane activator and calcium modulator (TACI), B-cell activating factor (BAFF-receptor), proliferation-inducing ligand (APRIL), cytotoxic T lymphocyte-associated protein-4-inducible co-stimulator (CTLA4-ICOS) and recombinant activating gene (RAG1), polymorphism, which could be associated a higher risk of presenting SIgAD, coeliac disease, and CVID.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,4,6–10</span></a> In addition to sharing genetic defects, familial aggregation and the known risk of SIgAD progressing to CVID suggest that they are probably part of a wide spectrum of the same disease.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,11</span></a> Furthermore, certain haplotypes HLA (A1, A29, B8, B14, DR3, DQ2) have been associated with a greater risk of SIgAD, although this association is not clear because these haplotypes are also associated with the autoimmune diseases frequently associated with this defect.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,12–14</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Most patients (85%–90%) affected by SIgAD are asymptomatic. The clinical signs of symptomatic patients are wide ranging, including recurrent sinopulmonary infections, infections and gastrointestinal disorders, allergies, autoimmune processes and neoplasias, with more frequency than the general population.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,5,15,16</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although the diagnosis of SIgAD is usually made by analysis of serum immunoglobulins during the evaluation of recurrent respiratory infections, many other cases are diagnosed “accidentally”, as part of a laboratory evaluation for coeliac disease, allergy, or autoimmune disease.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Prevalence of SIgAD is high among family members, and no studies have as yet been undertaken to compare the clinical and/or immunological difference among familial (FC) and sporadic (SC) cases. As a result, the severity, prognosis and need for complementary tests cannot be assessed. In this context, we set out to evaluate the prevalence of SIgAD in first-degree relatives (FDR) of SIgAD patients, determine whether screening family members is a useful strategy in the clinical management of this pathology, and compare the clinical and immunological characteristics in children diagnosed with sporadical SIgAD with those cases where there is an affected first-degree relative (FDR).</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study population</span><p id="par0025" class="elsevierStylePara elsevierViewall">A descriptive cross-sectional study was carried out from October 2010 to September 2011. All patients with SIgAD and their FDRs diagnosed and/or followed-up at the Paediatric Unit of Infectious Pathology and Immunodeficiencies of the Hospital Universitari Vall d’Hebron in Barcelona who met inclusion criteria were selected for the study. These patients were diagnosed, either because they had clinical signs or incidentally when studying other pathologies, such as allergic or autoimmune diseases.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Study protocol</span><p id="par0030" class="elsevierStylePara elsevierViewall">A questionnaire was administered to all participants by the same researcher. The information collected included demographic data (age, sex, consanguinity) and clinical signs (infections, allergies, autoimmunity, respiratory, gastrointestinal, dermatologic pathology and neoplasia), blood samples were collected for complete blood count, study of immunoglobulins and subclasses of serum IgG, antinuclear antibodies (ANA), isohaemaglutinines, antistreptolysin O (ASLO) and vaccine response against tetanus, measles, mumps, rubella, <span class="elsevierStyleItalic">Haemophilus influenzae (H. influenzae) b</span> and <span class="elsevierStyleItalic">Streptococcus pneumoniae (S. pneumoniae).</span> In family screening, complete blood count and immunoglobulins were included (IgG, IgA and IgM). This study was approved by the ethics committee of the hospital.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Inclusion criteria and definitions</span><p id="par0035" class="elsevierStylePara elsevierViewall">Paediatric patients aged between 4 and 8 years with final diagnosis of SIgAD according to the criteria of the ESID and PAGID<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> were included together with their FDRs, whose families all agreed to participate and signed the informed consent form.</p><p id="par0040" class="elsevierStylePara elsevierViewall">SIgAD was defined as a blood IgA level below 7<span class="elsevierStyleHsp" style=""></span>mg/dl (0.07<span class="elsevierStyleHsp" style=""></span>g/l) with normal IgG and IgM levels and normal antibody response in patients over 4 years of age.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">FC was defined as a patient diagnosed or followed-up by our unit in whom family screening showed there to be one member of the same family affected. If only the index case was affected, it was considered as SC.</p><p id="par0050" class="elsevierStylePara elsevierViewall">First-degree relatives with SIgAD were denominated as affected FDR (FDR-A) and relatives in whom no SIgAD was detected were classified as healthy FDR (FDR-H).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Laboratory studies</span><p id="par0055" class="elsevierStylePara elsevierViewall">Haematological and biochemical parameters were obtained through routine lab methods. Immunoglobulins (Ig) were determined though nephelometry, IgG subclasses through nephelometry with monoclonal antibodies (MoAb) and vaccine response in patients immunised through conventional serological methods.</p><p id="par0060" class="elsevierStylePara elsevierViewall">They were described as serum concentrations of immunoglobulins (IgM, IgG, IgA, IgE), subclasses of IgG, and decreased isohaemagglutinins and antistreptolysins when they were at least 2 standard deviations (SD) below the mean of the age-adjusted reference values established by Jollif et al.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> for the subject. ASLO values <200<span class="elsevierStyleHsp" style=""></span>UI/ml and isohaemaglutinines below 1/32 were considered negative, both for IgM and for IgG. The vaccine response was considered negative in cases with prior confirmation of the applicable vaccination and certain values below the cut point of our centre. ANA values were considered pathological when they were above 1/80.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Statistical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Fisher's exact test was used for the analysis of qualitative data, and the Student's <span class="elsevierStyleItalic">t</span> test for quantitative variables, with 5% significance. For the bivariate analysis, odds ratios (OR) were calculated. The statistical analysis was carried out using SPSS (SPSS Statistics for Windows, Version 17.0, SPSS Inc., Chicago, USA).</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Sociodemographic characteristics</span><p id="par0070" class="elsevierStylePara elsevierViewall">The sample included 130 participants, 42 cases and 88 FDRs (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">The mean age<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD of cases with SIgAD was 11 years<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.54 and 57% were female, with no differences found between FCs and SCs (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.17 and 0.10, respectively). The mean age of FDRs was 34<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.85 years and 57% (50) were female. No case of consanguinity was collected.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Familial cases</span><p id="par0080" class="elsevierStylePara elsevierViewall">In 13 of the 42 patients with SIgAD (31%), 1 or more affected relatives were found. The frequency of SIgAD in FDRs was estimated as 1 case for each 6 family members. One mother, 1 brother and 2 sisters had a known previous diagnosis of SIgAD (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Of the familial cases diagnosed, 50% (7) were mothers, 21.4% (3) fathers, 14.3% (2) brothers and 14.3% (2) sisters (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.55; OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.96; 95% CI, 0.62–6.21). In other words, 22% mothers, 14.5% brothers and sisters and 10% fathers showed SIgAD. The sociodemographic, clinical and laboratory characteristics of each FDR-A are shown separately in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Taking an estimated prevalence of SIgAD of 1/600 in Caucasians as a representation of the sample, calculations showed that 6 relatives needed to be studied to find 1 FC with SIgAD.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Clinical manifestations</span><p id="par0090" class="elsevierStylePara elsevierViewall">All children with SIgAD presented some type of clinical manifestation. The recorded infections are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. Parasites were isolated in only 2 (6.9%) SCs with diarrhoea.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">As regards autoimmunity phenomena, only 1 case of Hashimoto thyroiditis was described. There were no neoplasias.</p><p id="par0100" class="elsevierStylePara elsevierViewall">No significant clinical differences were found between FCs and SCs. In fact, even infections were more frequent in SCs (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.045, OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.12; 95% CI, 0.01–0.98). In contrast, FCs presented more admissions for respiratory causes than SCs (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04, OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6, 95% CI, 1.05–34.15), which is not confirmed when assessing the total number of admissions (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><p id="par0105" class="elsevierStylePara elsevierViewall">When FDRs were assessed, no differences were found as regards clinical manifestations between both groups, except for the presence of digestive pathologies, significantly more frequent in FDR-As (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Ten FDRs had psoriasis (13.5%), all within the FDR-H group. All neoplasias reported were solid tumours with no differences between both groups.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">As a marker for clinical severity, the need for hospital admission and chronic treatment was estimated. A significantly higher proportion of total admissions in FDR-As was shown with respect to FDR-Hs, with an increased overall risk of admission 4 times higher. The reasons for admission in FDR-As were infectious causes (2), respiratory (2) and 1 case secondary to digestive pathology. In FDR-Hs, 8 of the 9 admissions were caused by infections and the remainder by digestive pathology. Furthermore, 5 times more FDR-As needed chronic than FDR-Hs (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). In FDR-As, most (7) were due to digestive pathology and the rest received chronic treatment for respiratory (2) and allergic (1) pathology. The usual treatment reported in FDR-Hs was for gastrointestinal alterations in 12 cases (52%), for respiratory pathology in 7 (31%) cases, and for allergies in 4 (17%) cases.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Laboratory studies</span><p id="par0115" class="elsevierStylePara elsevierViewall">The levels of immunoglobulins, total leukocytes, lymphocytes and neutrophils of cases and FDRs are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>. IgG, IgM and IgE were significantly higher in FCs than SCs (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.007, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01, respectively). One patient from each group presented low levels of IgG subclasses (both IgG2). The humoral response was very similar in both groups and is shown in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>.</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Despite the fact that there are no differences in IgG and IgM levels between both groups of FDRs, 3 cases of hypogammaglobulinaemia G were detected in FDR-As and none in FDR-H cases (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0125" class="elsevierStylePara elsevierViewall">We found no evidence of the presence of more severe clinical phenotypes in familial cases of SIgAD in our series. We were only able to prove a clearly higher risk of admission due to respiratory pathology (most for asthma) in FCs, which could indicate a more severe phenotype; however, this was not confirmed when making an overall assessment of admissions for any cause in both groups.</p><p id="par0130" class="elsevierStylePara elsevierViewall">In any event, a number of factors must be taken into consideration. Although patients with SIgAD are asymptomatic in most of the series reported in the literature,<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,19</span></a> in our study all patients reported some kind of clinical sign, possibly due to selection bias in the centre where they received treatment. This may have contributed to the absence of significant clinical differences in our sample. On the other hand, loss of information is always a risk in retrospective studies, especially as regards minor clinical manifestations such as mild infections.</p><p id="par0135" class="elsevierStylePara elsevierViewall">The distribution of infection by type did not differ to that reported in the literature<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5,16</span></a> and, despite the fact that overall infections were more frequent in SCs, there were no differences in the need for hospital admission, which implies a mild course in both groups. The low prevalence of allergic processes and intestinal, autoimmune and tumoral pathology in our sample compared with other series<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1,2,15,16,19–24</span></a> — probably related to the fact that it is a paediatric population — prevents us from reaching conclusions as regards the role of familial aggregation as a risk factor for developing this type of pathology. However, the high prevalence of positive ANA in patients in both groups with no evident autoimmune manifestations was striking and could be related to SIgAD as an epiphenomenon of autoimmune disorders that can increase the risk of developing an autoimmune disorder in adulthood, or as part of a compensatory response to infection and to a sustained condition, as shown by Fusaro et al.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> Likewise, total IgE levels were also higher in FCs despite not presenting a higher prevalence of clinically significant allergic processes.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Serum concentrations of IgG and IgM were significantly higher in FCs. There was no obvious reason for this, as prevalence of severity of infection or inflammation was not higher in this group.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Humoral response, measured through isohaemagglutinins and titres of ASLO, was poor in a significant number of patients (3 FCs and 6 SCs), so it would be convenient to make these determinations in all cases. The response to vaccines included in our vaccination schedule (tetanus, measles, mumps, rubella, <span class="elsevierStyleItalic">H. influenzae</span> and <span class="elsevierStyleItalic">S. pneumoniae</span>) was good in both groups, unlike the measles vaccine, where bad response was only reported in FCs. Irrespective of their group, we consider that these patients must be closely followed-up to assess whether these findings can predict the development of more clinically significant immunodeficiencies such as CVID, as reported in other publications.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">As regards the usefulness of family screening, it seems reasonable to affirm that patients detected based on the familial screening of paediatric patients with SIgAD present sufficiently significant clinical symptomatology to justify this strategy, particularly considering the high prevalence of familial cases shown in this and other studies.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3,26,27</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Thus, the most significant risk factor for the development of SIgAD shown in previous studies is the existence of a positive family history.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> Due to ethnicity-related genetic difference, the prevalence of affected family members no doubt differs in different regions of the world.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> In our analysis, the frequency of one or more FDR affected was 16%, diagnosed <span class="elsevierStyleItalic">de novo</span> in more than 70% of relatives. There was more than 1 case in the same family in 31% of cases. This percentage is similar to other series, which estimate figures of up to 32.4%, with an elevated prevalence of consanguinity not found in our sample<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> and considerably higher than the general population, with a prevalence among Caucasians of 1 case in every 600.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Our study shows that the risk of SIgAD in FDRs of patients with this pathology was slightly higher in mothers (22%) than fathers (10%) and siblings (14.5%), although no major variations were found. These data are not consistent with previous studies, which report a higher risk in siblings.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3,27,28</span></a> Vorechovský et al.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> analysed serum concentrations of Ig in close relatives of Swedish patients with SIgAD and CVID, estimating the relative risk for the siblings of patients with SIgAD to be approximately 50. However, parent of origin penetrance differences have been found in the transmission of SIgAD to children.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> Some investigations have found a higher prevalence of children with SIgAD born from mothers with this pathology than from fathers with the same defect.<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">28,30</span></a> This type of inheritance with more predominance in maternal transmission could be related to mitochondrial defects and could explain in part the higher percentage of affected mothers found in our study, since the number of siblings (one brother/sister for each mother) is small in relation to other studies.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3,27</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Despite the fact that in our study only 14% of FDR-As were asymptomatic, this did not differ significantly from FDR-Hs, which is why it could be assumed that pathologies reported in FDR-As were similar to those in the general population. In 2008, Aghamohammadi et al.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> presented a study which affirmed that all relatives of patients with SIgAD who also had this defect were asymptomatic; however, they were not compared with the cohort of healthy relatives, which may explain our results. A recent case–control study comparing the symptoms of SIgAD patients with those of healthy patients found higher rates of infections, allergic phenomena and autoimmunity in patients with SIgAD<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a>; we were unable to confirm this in our series. However, taking hospital admissions and need for chronic treatment as a marker of clinical severity would support the finding of Jorgensen et al.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Although we were unable to show the significantly lower levels of IgG and IgM reported by other authors, who propose these variables as markers of risk for evolution to CVID, we detected 3 adult patients with hypogammaglobulinaemia who should be studied thoroughly.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3,27</span></a> These findings, however, cannot be fully validated because IgG subclasses and antibody levels in family members were not evaluated.</p><p id="par0175" class="elsevierStylePara elsevierViewall">In conclusion, we consider that the elevated prevalence of SIgAD in FDRs of patients with this pathology associated with a greater clinical severity, measured indirectly through admission rates and the need for chronic treatment, shows FDRs could benefit from screening programmes. Since few relatives will need to be screened to find one positive case, this could be a cost-effective prevention strategy. This would enable individuals with this type of immunodeficiency to start treatment or prophylaxis measures to prevent hospitalisation, or to simply attend regular check-ups due to the risk of evolution to CVID.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Authors’ contribution</span><p id="par0180" class="elsevierStylePara elsevierViewall">P. Soler-Palacín and E. Cobos-Carrascosa have contributed equally to the study.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicts of interest</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors declare that there are no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres600554" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Patients and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec614800" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres600553" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Pacientes y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec614799" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study protocol" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Inclusion criteria and definitions" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Laboratory studies" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Sociodemographic characteristics" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Familial cases" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Clinical manifestations" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Laboratory studies" ] ] ] 7 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0070" "titulo" => "Authors’ contribution" ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-03-09" "fechaAceptado" => "2015-04-16" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec614800" "palabras" => array:5 [ 0 => "IgA deficiency" 1 => "Autoimmunity" 2 => "Familial cases" 3 => "Infections" 4 => "Screening" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec614799" "palabras" => array:5 [ 0 => "Déficit selectivo inmunoglobulina A" 1 => "Autoinmunidad" 2 => "Casos familiares" 3 => "Infecciones" 4 => "Cribado" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Selective immunoglobulin A deficiency (SIgAD), the most common primary immunodeficiency, is often asymptomatic. High rates of familial clustering have been described in SIgAD, but the causative genetic defect and mechanism of inheritance are unknown.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To determine whether familial SIgAD cases show more severe clinical and immunological characteristics than sporadic ones; to investigate the utility of screening first-degree relatives (FDRs) of these patients, and to determine whether symptoms in affected family members are important enough to justify screening.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Patients and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Descriptive, cross-sectional study (October 2010–September 2011) of all patients with SIgAD followed up in our centre. Demographic, clinical, and analytical data were reviewed. A familial case was defined as an SIgAD patient with at least 1 affected FDR.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Of the 130 participants, 42 were SIgAD patients and 88 FDR. There were 13 (31%) familial cases and 14 (16%) affected FDRs. Six family members had to be studied in order to detect 1 affected member. There were no clinical differences between familial and sporadic SIgAD cases. The percentages of intestinal disease (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001, OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9.57, 95% <span class="elsevierStyleSmallCaps">CI</span> 2.59–35.3), hospitalisations (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.045, OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4.01; 95% CI 1.10–14.67], and need for chronic treatment (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.006, OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5.5; 95% CI 1.57–19.54) were higher in affected FDRs than in unaffected ones.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The symptoms were not more severe in familial than sporadic SIgAD cases. Nonetheless, the elevated prevalence of affected FDRs with significant morbidity may justify routine screening of close family members of these patients.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Patients and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducción</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El déficit selectivo de IgA (DSIgA) es la inmunodeficiencia primaria más frecuente, siendo a menudo asintomática. Se ha descrito una elevada agregación familiar, sin conocerse el defecto genético causante ni su mecanismo hereditario.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Definir la utilidad del cribado de los familiares de primer grado de los pacientes con DSIgA valorando si los casos familiares presentan unas características clínicas e inmunológicas más graves que los casos esporádicos (CE) y si los familiares diagnosticados de DSIgA presentan sintomatología clínica significativa para justificar su cribado.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Pacientes y métodos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio transversal descriptivo (octubre del 2010-septiembre del 2011) de todos los pacientes con DSIgA controlados en nuestro centro, con revisión de datos demográficos, clínicos y analíticos. Se consideró como caso familiar (CF) todo aquel con al menos un familiar de primer grado (FPG) con DSIgA.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">De los 130 participantes, 42 eran pacientes con DSIgA y 88 FPG. Se diagnosticaron 13 CF (31%), 29 CE (69%) y 14 (16%) FPG enfermos (FPG-E). El número necesario a analizar para encontrar un FPG-E fue de 6 familiares. No hubo diferencias clínicas entre los pacientes. Hubo una proporción mayor de patología intestinal (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,001, OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9,57, IC del 95%, 2,59–35,3), ingresos (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,045, OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4,01; IC del 95%, 1,10–14,67) y necesidad de tratamiento crónico (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,006, OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5,5; IC del 95%, 1,57–19,54) en los FPG-E con respecto a los FPG sanos.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">A pesar de no encontrar más complicaciones clínicas en los CF de DSIgA, la elevada prevalencia de familiares afectados con afectación clínica significativa podría justificar la realización sistemática de estos programas de cribado.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Pacientes y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0045">Please cite this article as: Soler-Palacín P, Cobos-Carrascosa E, Martín-Nalda A, Caracseghi F, Hernández M, Figueras-Nadal C. ¿Es útil el cribado familiar en el déficit selectivo de inmunoglobulina A? An Pediatr (Barc). 2016;84:70–78.</p>" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2076 "Ancho" => 2809 "Tamanyo" => 217626 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Description of the studied sample. IC: index case; SIgAD: selective IgA deficiency; FDR: first-degree relatives; SC: sporadic case; FC: familial case; FDR-A: affected first-degree relatives; FDR-H: healthy first-degree relatives.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No. \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Familial relationship \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Known case<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age (years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Symptoms \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IgA<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IgM<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IgG<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sister \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, allergy and infections \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><7 (30–200) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">240 (50–200) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.155 (600–1230) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Brother \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><7 (30–200) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">163 (50–200) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.450 (600–1230) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mother \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, Crohn's disease and infections \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><7 (70–400) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92 (40–230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.191 (700–1600) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mother \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, allergy and infections \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><7 (70–400) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">172 (40–230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">871 (700–1600) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mother \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, autoimmunity (thyroiditis) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 (70–400) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74 (40–230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">687<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> (700–1600) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mother \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, allergy and infections \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (70–400) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">212 (40–230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.143 (700–1600) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mother \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, coeliac disease and dermatological \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><7 (70–400) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74 (40–230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.637 (700–1600) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mother \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, respiratory and infections \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><7 (70–400) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">130 (40–230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.316 (700–1600) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mother \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, allergic and tumoral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><7 (70–400) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 (40–230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.555 (700–1600) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Father \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 (70–400) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">104 (40–230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">553<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> (700–1600) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Father \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, infections \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><7 (70–400) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 (40–230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.275 (700–1600) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Father \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, digestive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 (70–400) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 (40–230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">620<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> (700–1600) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Brother \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, infections and respiratory \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><7 (70–400) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92 (50–200) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.280 (600–1230) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sister \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, infections and respiratory \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><7 (30–200) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">126 (40–230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.516 (700–1600) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab982553.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Relative diagnosed before the study.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Normal serum immunoglobulins figures taken from Jollif et al.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a></p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Patients with hypogammaglobulinaemia IgG.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Sociodemographic clinical and laboratory characteristics of ill first-degree relatives (FDR-A).</p>" ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">SC: sporadical cases; FC: familial cases; CI: confidence interval; OR: odds ratio.</p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Bold values are statistically significant.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Familial case(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>13), <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sporadic case(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>29), <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Infections</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (76.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 (96.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.045</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.12 (0.01–0.98) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Upper respiratory tract infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (69.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 (96.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.026</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 (0.01–0.81) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lower respiratory tract infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (69.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 (79.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.478 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.59 (0.13–2.58) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diarrhoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (15.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (31.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.453 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.40 (0.07–2.18) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Admission \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (30.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (34.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.84 (0.20–3.50) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Allergies</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (46.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (41.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.21 (0.32–4.60) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Atopic dermatitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (30.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (20.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.697 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.70 (0.38–7.56) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Urticaria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (7.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (17.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.647 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.40 (0.04–3.69) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (15.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (17.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.87 (0.14–5.33) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Respiratory pathology</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (76.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 (79.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.87 (0.18–4.27) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Asthma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (76.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 (79.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.87 (0.18–4.27) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Interstitial pneumopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (3.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 (–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Bronchiectasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (3.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 (–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (23.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (41.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.314 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.42 (0.10–1.87) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Admission \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (30.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (6.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.040</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.00 (1.05–34.15) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Autoimmunity</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (3.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 (–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Antinuclear antibodies + \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (38.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 (51.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.514 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.58 (0.15–2.24) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Digestive pathology</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (46.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (27.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.298 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.25 (0.58–8.79) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Inflammatory bowel disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (3.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 (–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Coeliac disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (3.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 (–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic diarrhoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (30.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (20.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.697 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.70 (0.38–7.56) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (46.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (27.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.298 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.25 (0.58–8.79) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Dermatological pathology</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (30.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (24.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.713 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.40 (0.32–6.06) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Alopecia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (7.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.310 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 (–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vitiligo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (3.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 (–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Total admissions</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (61.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (41.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.192 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.2 7 (0.59–8.65) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab982550.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Fisher's exact test.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of FCs and SCs.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">FDR-A: affected first-degree relatives; FDR-H: healthy first-degree relatives; CI: confidence interval; OR: odds ratio.</p><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Bold values are statistically significant.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FDR-A(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>14), <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FDR-H(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>74), <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Asymptomatic</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (14.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 (27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.45 (0.09–2.19) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Infections</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (64.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 (44.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.13 (0.94–1.37) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Upper respiratory tract infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (64.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 (43.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.124 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.36 (0.72–7.73) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lower respiratory tract infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (57.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 (28.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.039</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.37 (1.04–10.87) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diarrhoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (21.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (10.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.18 (0.81–1.71) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Allergies</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (50.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 (41.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.05 (0.87–1.27) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Atopic dermatitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (28.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (12.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.25 (0.86–1.82) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Urticaria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (21.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (16.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.06 (0.81–1.39) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Respiratory pathology</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (35.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 (20.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.24 (0.89–1.70) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Asthma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (28.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 (17.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.12 (0.85–1.49) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cystic fibrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (7.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (1.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.69 (0.42–6.81) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Autoimmunity</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (21.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (10.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.18 (0.81–1.71) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Thyroiditis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (7.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (6.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.02 (0.82–1.93) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rheumatoid arthritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (7.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (2.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.27 (0.56–2.84) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Neoplasias</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (14.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (8.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.13 (0.75–1.71) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Digestive pathology</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (9.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.001</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.57 (2.59–35.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Inflammatory bowel disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (14.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.02</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 (–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Coeliac disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (14.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.02</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 (–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic diarrhoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (21.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (9.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.70 (0.38–7.56) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Dermatological pathology</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (35.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (16.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.24 (0.89–1.70) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Alopecia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (1.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 (–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vitiligo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (7.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 (–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Total admissions</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.045</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.01 (1.10–14.67) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Chronic treatment</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 (31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.006</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.5 (1.57–19.54) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab982551.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Fisher's exact test.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of FDR-Hs and FDR-As.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">SC: sporadical cases; FC: familial cases; SD: standard deviation; SIgAD: selective IgA deficiency; FDR: first-degree relatives; FDR-A: affected FDR; FDR-H: Healthy FDR.</p><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Bold values are statistically significant.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Children with SIgAD</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">FDR</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FCAverage<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SCAverage<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FDR-AAverage<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FDR-HAverage<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Leukocytes (cel/mm<span class="elsevierStyleSup">3</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.369<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.689 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.050<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.110<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.769 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7573 (2233) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.47 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Lymphocytes (cel/mm<span class="elsevierStyleSup">3</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.538<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>961 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.788<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.068 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.208<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>503 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.557<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>838 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Neutrophils (cel/mm<span class="elsevierStyleSup">3</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.915<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.446 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.263<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.404 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.954<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.726 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4218<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.810 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">IgM (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">162 (105) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.007</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">115<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">120<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.79 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">IgG (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.417<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>308 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.203<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>308 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.04</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.232<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>518 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.003<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>182 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">IgA (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.5<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">169<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><<span class="elsevierStyleBold">0.001</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">IgE (UI/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">430<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.103 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">102<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>189 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.01</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab982552.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0030" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Student's <span class="elsevierStyleItalic">t</span> test.</p>" ] 1 => array:3 [ "identificador" => "tblfn0035" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0035">4 cases of partial deficiency with IgA levels from 10 to 23<span class="elsevierStyleHsp" style=""></span>mg/dl.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Complete blood count and serum concentrations of immunoglobulins in FC vs. SC and FDR-H vs. FDR-A.</p>" ] ] 5 => array:7 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Familial case, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sporadic case, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Tetanus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (4)/25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.69 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Measles \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (17)/12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mumps \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (17)/10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (4)/22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Rubella \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (7.7)/11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.29 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Haemophilus influenzae b</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pneumococcal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">ASLO (<200<span class="elsevierStyleHsp" style=""></span>UI/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1(11)/9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (33)/15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.35 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Isohaemaglutinines (<1/32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (15)/4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (7)/7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.71 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab982549.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0040" "etiqueta" 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 11 | 15 |
| 2024 October | 47 | 37 | 84 |
| 2024 September | 56 | 35 | 91 |
| 2024 August | 58 | 51 | 109 |
| 2024 July | 46 | 30 | 76 |
| 2024 June | 41 | 19 | 60 |
| 2024 May | 35 | 35 | 70 |
| 2024 April | 57 | 34 | 91 |
| 2024 March | 47 | 25 | 72 |
| 2024 February | 47 | 24 | 71 |
| 2024 January | 44 | 20 | 64 |
| 2023 December | 36 | 20 | 56 |
| 2023 November | 44 | 22 | 66 |
| 2023 October | 28 | 21 | 49 |
| 2023 September | 24 | 21 | 45 |
| 2023 August | 32 | 25 | 57 |
| 2023 July | 40 | 19 | 59 |
| 2023 June | 32 | 27 | 59 |
| 2023 May | 56 | 29 | 85 |
| 2023 April | 50 | 12 | 62 |
| 2023 March | 75 | 24 | 99 |
| 2023 February | 40 | 8 | 48 |
| 2023 January | 31 | 19 | 50 |
| 2022 December | 61 | 40 | 101 |
| 2022 November | 57 | 38 | 95 |
| 2022 October | 52 | 35 | 87 |
| 2022 September | 62 | 20 | 82 |
| 2022 August | 65 | 33 | 98 |
| 2022 July | 75 | 37 | 112 |
| 2022 June | 52 | 50 | 102 |
| 2022 May | 55 | 35 | 90 |
| 2022 April | 36 | 40 | 76 |
| 2022 March | 35 | 39 | 74 |
| 2022 February | 35 | 16 | 51 |
| 2022 January | 43 | 37 | 80 |
| 2021 December | 31 | 34 | 65 |
| 2021 November | 38 | 47 | 85 |
| 2021 October | 38 | 50 | 88 |
| 2021 September | 25 | 36 | 61 |
| 2021 August | 31 | 39 | 70 |
| 2021 July | 37 | 24 | 61 |
| 2021 June | 52 | 27 | 79 |
| 2021 May | 45 | 27 | 72 |
| 2021 April | 94 | 86 | 180 |
| 2021 March | 48 | 32 | 80 |
| 2021 February | 26 | 23 | 49 |
| 2021 January | 23 | 23 | 46 |
| 2020 December | 27 | 23 | 50 |
| 2020 November | 20 | 14 | 34 |
| 2020 October | 20 | 24 | 44 |
| 2020 September | 40 | 21 | 61 |
| 2020 August | 14 | 28 | 42 |
| 2020 July | 22 | 35 | 57 |
| 2020 June | 30 | 16 | 46 |
| 2020 May | 34 | 25 | 59 |
| 2020 April | 25 | 17 | 42 |
| 2020 March | 37 | 15 | 52 |
| 2020 February | 24 | 12 | 36 |
| 2020 January | 26 | 20 | 46 |
| 2019 December | 59 | 24 | 83 |
| 2019 November | 22 | 14 | 36 |
| 2019 October | 46 | 17 | 63 |
| 2019 September | 33 | 14 | 47 |
| 2019 August | 60 | 17 | 77 |
| 2019 July | 25 | 25 | 50 |
| 2019 June | 32 | 18 | 50 |
| 2019 May | 49 | 35 | 84 |
| 2019 April | 64 | 27 | 91 |
| 2019 March | 37 | 17 | 54 |
| 2019 February | 43 | 20 | 63 |
| 2019 January | 48 | 18 | 66 |
| 2018 December | 48 | 29 | 77 |
| 2018 November | 132 | 29 | 161 |
| 2018 October | 219 | 40 | 259 |
| 2018 September | 108 | 32 | 140 |
| 2018 August | 18 | 0 | 18 |
| 2018 July | 2 | 0 | 2 |
| 2018 June | 3 | 0 | 3 |
| 2018 May | 4 | 0 | 4 |
| 2018 April | 92 | 0 | 92 |
| 2018 March | 16 | 0 | 16 |
| 2018 February | 7 | 0 | 7 |
| 2018 January | 8 | 0 | 8 |
| 2017 December | 12 | 0 | 12 |
| 2017 November | 13 | 0 | 13 |
| 2017 October | 8 | 0 | 8 |
| 2017 September | 7 | 0 | 7 |
| 2017 August | 10 | 0 | 10 |
| 2017 July | 6 | 0 | 6 |
| 2017 June | 22 | 9 | 31 |
| 2017 May | 23 | 9 | 32 |
| 2017 April | 8 | 28 | 36 |
| 2017 March | 7 | 9 | 16 |
| 2017 February | 9 | 2 | 11 |
| 2017 January | 7 | 0 | 7 |
| 2016 December | 22 | 9 | 31 |
| 2016 November | 23 | 4 | 27 |
| 2016 October | 26 | 4 | 30 |
| 2016 September | 32 | 7 | 39 |
| 2016 August | 34 | 8 | 42 |
| 2016 July | 19 | 4 | 23 |
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