Gene Signature of Regulatory T Cells Isolated from Children with Selective IgA Deficiency and Common Variable Immunodeficiency.

Selective IgA deficiency (SIgAD) is the most common form and common variable immunodeficiency (CVID) is the most symptomatic form of predominant antibody deficiency. Despite differences in the clinical picture, a similar genetic background is suggested. A common feature of both disorders is the occurrence of autoimmune conditions. Regulatory T cells (Tregs) are the major immune cell type that maintains autoimmune tolerance. As the different types of abnormalities of Treg cells have been associated with autoimmune disorders in primary immunodeficiency (PID) patients, in our study we aimed to analyze the gene expression profiles of Treg cells in CVID and SIgAD patients compared to age-matched healthy controls. The transcriptome-wide gene profiling was performed by microarray technology. As a result, we analyzed and visualized gene expression patterns of isolated population of Treg cells. We showed the differences at the gene level between patients with and without autoimmunizations. Our findings suggest that the gene signatures of Treg cells isolated from SIgAD and CVID patients differ from age-matched healthy controls and from each other, presenting transcriptional profiles enriched in innate immune or Th response, respectively. The occurrence of autoimmunity in both types of PID is associated with down-regulation of class I IFNs signaling pathways. In summary, our findings improve our understanding of Treg dysfunctions in patients with common PIDs and associated autoimmunity.

Doenças autoimunes e autoanticorpos em pacientes pediátricos e seus parentes de primeiro grau com deficiência de imunoglobulina / Autoimmune diseases and autoantibodies in pediatric patients and their first-degree relatives with immunoglobulin A deficiency

Introdução: As manifestações clínicas da deficiência de imunoglobulina A (DIgA) incluem infecções recorrentes, atopia e doenças autoimunes. No entanto, para o nosso conhecimento, as avaliações concomitantes de doenças autoimunes e autoanticorpos em uma coorte de pacientes com DIgA com idade atual > 10 anos e seus parentes não foram feitas. Objetivos: Avaliar doenças autoimunes e presença de autoanticorpos em pacientes com DIgA e seus parentes de primeiro grau. Métodos: Estudo transversal feito em 34 pacientes com DIgA (idade atual > 10 anos) e em seus parentes de primeiro grau. Todos foram acompanhados em um centro terciário brasileiro para imunodeficiência primária: 27 crianças/adolescentes e sete de seus parentes de primeiro grau com diagnóstico tardio de DIgA. Doenças autoimunes e autoanticorpos (anticorpos antinucleares, fator reumatoide e antitireoglobulina, antitiroperoxidase e anticorpos antiendomísio da classe IgA) também foram avaliadas. Resultados: Doenças autoimunes (n = 14) e/ou autoanticorpos (n = 10, quatro deles com autoanticorpos isolados) foram observadas em 18/34 (53%) dos pacientes e seus parentes. As doenças autoimunes mais comuns encontradas foram tireoidite (18%), artrite crônica (12%) e doença celíaca (6%). Os autoanticorpos mais frequentes foram anticorpos antinucleares (2%), antitireoglobulina e/ou antitireoperoxidase (24%). Nenhuma diferença significativa foi observada no sexo feminino, idade no momento do diagnóstico e idade atual em pacientes com DIgA com e sem doenças autoimunes e/ou presença de autoanticorpos (p > 0,05). As frequências de imunodeficiência de primárias na família, autoimunidade em família, atopia e infecções recorrentes foram semelhantes em ambos os grupos (p> 0,05). Conclusão: Doenças autoimunes e autoanticorpos foram observadas em pacientes com DIgA durante o acompanhamento, o que reforça a necessidade de um acompanhamento rigoroso e contínuo durante a adolescência e a idade adulta. .

Introduction: Clinical manifestations of Immunoglobulin A Deficiency (IgAD) include recur-rent infections, atopy and autoimmune diseases. However, to our knowledge, theconcomitant evaluations of autoimmune diseases and auto antibodies in a cohort of IgADpatients with current age >10 years and their relatives have not been assessed. Objectives: To evaluate autoimmune diseases and the presence of auto antibodies in IgADpatients and their first-degree relatives. Methods: A cross-sectional study was performed in 34 IgAD patients (current age >10years) and their first-degree relatives. All of them were followed at a tertiary Brazilianprimary immunodeficiency center: 27 children/adolescents and 7 of their first-degree rela-tives with a late diagnosis of IgAD. Autoimmune diseases and autoantibodies (antinuclearantibodies, rheumatoid factor, and anti-thyroglobulin, anti-thyroperoxidase and IgA classanti-endomysial antibodies) were also assessed. Results: Autoimmune diseases (n = 14) and/or autoantibodies (n = 10, four of them with iso-lated autoantibodies) were observed in 18/34 (53%) of the patients and their relatives. Themost common autoimmune diseases found were thyroiditis (18%), chronic arthritis (12%)and celiac disease (6%). The most frequent autoantibodies were antinuclear antibodies(2%), anti-thyroglobulin and/or anti-thyroperoxidase (24%). No significant differences wereobserved in the female gender, age at diagnosis and current age in IgAD patients with andwithout autoimmune diseases and/or presence of auto antibodies (p > 0.05). The frequen-cies of primary immunodeficiencies in family, autoimmunity in family, atopy and recurrentinfections were similar in both groups (p > 0.05). Conclusion: Autoimmune diseases and auto antibodies were observed in IgAD patients dur-ing follow-up, reinforcing the necessity of a rigorous and continuous follow-up duringadolescence and adulthood. .

RAD50 single-nucleotide polymorphism in predominantly antibody deficiency

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Alteration in humoral immunity is common among family members of patients with common variable immunodeficiency

Background: The prevalence of primary immunodeficiency (PID) in the relatives of patients with common variable immunodeficiency (CVID) and IgA deficiency is high. Allergic disorders have been recorded in patients with humoral immunodeficiency. We aimed to determine the frequency of humoral immunodeficiency and atopy in the relatives of patients with CVID. Methods: The study population comprised 20 CVID patients and their relatives. All relatives were screened using a questionnaire covering demographic characteristics, warning signs of PID (adults and children), and core questions on asthma, rhinitis, and eczema from the International Study of Asthma and Allergies in Childhood (ISAAC). We also recorded absolute neutrophil and lymphocyte counts, serum immunoglobulin levels, pulmonary function values, and skin prick test results. Results: The study sample comprised 20 patients with CVID (15 males, 5 females; mean [SD] age, 16.4 [9] years) and 63 first-degree relatives (18 mothers, 16 fathers, 16 sisters, 10 brothers, and 3 offspring). The rate of parental consanguinity was 75%. Of 17 family members with positive PID warning signs, 6 had concomitant hypogammaglobulinemia (3 low IgM levels, 2 selective IgA deficiency, and 1 partial IgA deficiency). The ISAAC questionnaire revealed allergic rhinitis in 3 mothers, asthma in 2 fathers, and 1 sibling. Skin prick testing revealed sensitization to aeroallergens in 31.6% of cases in addition to 1 parent and 1 sibling. Conclusions: Almost half of the 20 families with a CVID patient had at least 1 additional member with hypogammaglobulinemia, leading us to recommend routine screening for relatives of CVID patients (AU)

Antecedentes: Es conocida la alta prevalencia de inmunodeficiencias entre los familiares de pacientes con inmunodeficiencia común variable (IDCV) y con déficit de IgA. Por otro lado, también se han descrito enfermedades alérgicas en pacientes con inmunodeficiencias humorales. El objetivo de este estudio ha sido el determinar la frecuencia de inmunodeficiencias humorales y de atopia entre los familiares de pacientes con IDCV. Métodos: Se estudiaron familiares de pacientes con IDCV. Todos los miembros de la familias fueron seleccionadas por un cuestionario que incluyó la determinación de las características demográficas, las señales de alarma, en adultos y niños, de padecer inmunodeficiencias primarias (IDP) y preguntas del Estudio Internacional de Asma y Alergia en la Infancia (ISAAC) para el asma, la rinitis y el eczema. Además, se realizaron estudios analíticos sobre el contaje de neutrófilos y linfocitos, los niveles de inmunoglobulinas séricas, la función pulmonar y pruebas cutáneas prick. Resultados: Se determinaron veinte casos de IDCV (15M, 5F, edad media: 16,4 ± 9 años) y se estudiaron un total de 63 parientes de primer grado (18 madres, 16 padres, 16 hermanas, 10 hermanos y 3 descendientes). La tasa de consanguinidad de los padres fue de 75%. En general, entre los 17 miembros de la familia con señales de alarma de padecer IDP, 6 tenían hipogammaglobulinemia concomitante; 3 bajos niveles de IgM, 2 selectivos y 1 con parcial déficit de IgA. El cuestionario ISAAC reveló rinitis alérgica en 3/18 de las madres; mientras que, el asma, en 2/18, de padres y de 1/26 de los hermanos. Finalmente, en las pruebas de punción cutánea se obtuvo una sensibilización a aeroalérgenos en el 31,6% de los casos, pero en ninguno de sus padres, hermanos o descendientes. Conclusiones: En 20 familias de pacientes con IDCV, casi la mitad de sus miembros tenían al menos un individuo con hipogammaglobulinemia, por lo que recomendamos una exploración rutinaria entre todos los familiares de pacientes con IDCV(AU)

Doença de Graves e deficiência de IgA como manifestações da síndrome de deleção 22q11.2 / Graves disease and IgA deficiency as manifestations of 22q11.2 deletion syndrome:

A síndrome de deleção 22q11.2 (SD22q11.2) está associada à alta variabilidade fenotípica, abrangendo o espectro velocardiofacial/síndrome de DiGeorge. Manifestações autoimunes, endocrinológicas e de imunodeficiência vêm sendo relatadas associadas à síndrome. O objetivo deste estudo foi relatar um caso de SD22q11.2 associado à deficiência de IgA e à doença de Graves e rever a literatura visando verificar a frequência dessas alterações na SD22q11.2. Os distúrbios autoimunes, cada vez mais relacionadas a SD22q11.2 e novos fenótipos, vêm sendo incorporadas ao seu espectro clínico. No presente estudo, verificou-se que a doença de Graves associada à SD22q11.2 foi relatada em apenas dezesseis pacientes e quinze descritos na literatura nos últimos 13 anos. Com base na incidência e na amplitude de seu espectro de manifestações já reconhecidas, reforçaram-se os achados da literatura de que a doença de Graves deve ser incluída nas manifestações da SD22q11.2, o que nos levaria a pesquisá-la nos portadores da deleção 22q11.2.

The 22q11.2 deletion syndrome (22q11.2DS) is related to a high phenotypic variability including the velocardiofacial/DiGeorge spectrum. Autoimmune, endocrine and immunodeficiency manifestations have been reportedly associated with the syndrome. The objective of this study was to report a case of 22q11.2DS associated with IgA deficiency and Graves disease and review literature in order to verify the frequency of syndrome alterations. Autoimmune disorders have been increasingly related to 22q11.2DS, and new phenotypes are being incorporated in the clinical spectrum of this syndrome. In our study we found that Graves disease in association with 22q11.2DS was reported in only sixteen patients, and fifteen cases were described in the last 13 years. Based on the incidence and on the amplitude of this recognized spectrum, we reinforce the findings of literature that Graves disease should be included on the 22q11.2DS manifestations, which would lead us to seek it with 22q11.2 deletion patients.

Deficiência de IgA / IgA deficiency

Objetivo: Estudar a deficiência de imunoglobulina A (IgA) nos aspectos clínicos, labaoratoriais e terapêuticos. Métodos: Revisäo bibliográfica dos últimos dez anos, abordando o tema por meio do sistema Medline e procura direta. Resultados e conclusöes: Por ser a imunodeficiência primária mais freqüente, com prevalência média de 1:700, a deficiência de IgA deve ser estudada em seus apectos clínicos, laboratoriais e terapêuticos pelo pediatra e subespecialistas pediátricos. As características clínicas da imunodeficiência total e parcial ou transitória devem ser conhecidas, assim como as complicaçöes e as técnicas laboratoriais, intuito de se estabelecer diagnóstico e prognóstico corretos.