Serum Protein Electrophoresis May Be Used as a Screening Tool for Antibody Deficiency in Children and Adolescents.

Background: Patients with antibody deficiency may experience exceptionally long diagnostic delays, increasing the risk of life-threatening infections, end-organ damage, mortality, and health costs. Objective: This study aimed to analyze serum protein electrophoresis and verify the correlation between calculated globulin (CG, total protein minus albumin levels) or electrophoretically determined serum gamma globulin fraction (Gamma) with IgG levels in children and adolescents under 18 years old (yo). Methods: We analyzed serum protein electrophoresis (GC or Gamma) and IgG levels from 1215 children and adolescents under 18 yo, classified into 5 age groups. We verified the correlation between CG or Gamma with serum IgG levels. Results: Serum IgG levels varied according to age groups (from 4.3 ± 2.3 g/l in children under 6 months old to 11.4 ± 3.2 g/l in adolescents in the 10-<18 yo group). CG sensitivity and specificity to detect IgG below the reference range for all patients were 93.1% and 81.8%, respectively, and varied according to age group. Gamma sensitivity and specificity for all patients were 100% and 87.8%, respectively, and varied according to age group as well. We found serum IgG levels below the age reference level in 29 patients (2.4% of the cases) using CG or Gamma levels. Conclusion: Both CG and Gamma levels may be of utility as a screening tool for earlier diagnosis of antibody deficiency in children and adolescents under 18 yo.

The Utility of IgA-Based Serologic Markers in Diagnosing Celiac Disease in Children 24 Months of Age or Younger.

Current screening guidelines in North America for celiac disease recommend additional IgG based testing for younger children. Our multicenter retrospective study showed that the anti-tissue transglutaminase IgA antibody test should be the recommended initial test in all children, including those ≤24 months of age.

Niveles de IgA en adultos con enfermedad celíaca / IgA levels in adults with celiac disease

La enfermedad celíaca (EC) es una enfermedad autoinmune sistémica desencadenada por el consumo de gluten de la dieta en personas con susceptibilidad genética. Los principales test serológicos utilizados para el diagnóstico y seguimiento de la EC son pruebas basadas en anticuerpos de isotipo inmunoglobulina (Ig) A, siendo la determinación de IgA anti-transglutaminasa tisular (tTG)2 la prueba serológica inicial de elección. La deficiencia selectiva de IgA (DSIgA), es más prevalente en pacientes con EC que en la población general, dificultando el diagnostico serológico de la enfermedad. En el presente estudio observacional descriptivo, se incluyeron 74 pacientes adultos con diagnóstico confirmado de EC y se determinó IgA anti-tTG2 en suero mediante ensayo de ELISA a fin de detectar a aquellos pacientes con niveles indeterminados o negativos, los cuales podrían presentar DSIgA. Se dosó IgA total en el suero de estos pacientes por inmunodifusión radial y el promedio fue de 237,8 ± 100,6 mg/dL. En una paciente del sexo femenino fue detectada IgA total menor a 7 mg/dL, con niveles séricos de IgG e IgM normales, característicos de la DSIgA. Así, la frecuencia calculada de DSIgA fue de 1,35% en la población con EC estudiada. En conclusión, este trabajo es una primera aproximación para describir la frecuencia de DSIgA en pacientes con EC del país y reafirma la importancia de incluir el dosaje de IgA total en el caso de realizar test serológicos de la EC basados en IgA(AU)

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. .

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

INTRODUCTION: Clinical manifestations of Immunoglobulin A Deficiency (IgAD) include recurrent infections, atopy and autoimmune diseases. However, to our knowledge, the concomitant evaluations of autoimmune diseases and autoantibodies in a cohort of IgAD patients with current age > 10 years-old and their relatives have not been assessed. OBJECTIVES: To evaluate autoimmune diseases and the presence of autoantibodies in IgAD patients and their first-degree relatives. METHODS: A cross-sectional study was performed in 34 IgAD patients (current age > 10 years-old) and their first-degree relatives. All of them were followed at a tertiary Brazilian primary immunodeficiency center: 27 children/adolescents and 7 of their first-degree relatives with a late diagnosis of IgAD. Autoimmune diseases and autoantibodies (antinuclear antibodies, rheumatoid factor, and anti-thyroglobulin, anti-thyroperoxidase and IgA class anti-endomysial antibodies) were also assessed. RESULTS: Autoimmune diseases (n=14) and/or autoantibodies (n=10, four of them with isolated autoantibodies) were observed in 18/34 (53%) of the patients and their relatives. The most 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 were observed in the female gender, age at diagnosis and current age in IgAD patients with and without autoimmune diseases and/or presence of autoantibodies (p>0.05). The frequencies of primary immunodeficiency's in family, autoimmunity in family, atopy and recurrent infections were similar in both groups (p>0.05). CONCLUSION: Autoimmune diseases and autoantibodies were observed in IgAD patients during follow-up, reinforcing the necessity of a rigorous and continuous follow-up during adolescence and adulthood.

Immunoglobulin deficiencies: the B-lymphocyte side of DiGeorge Syndrome.

DiGeorge syndrome is associated with a T-lymphocyte immunodeficiency. The prevalence of hypogammaglobulinemia has not been reported. We found that 3% of patients with DiGeorge syndrome were receiving immunoglobulin replacement therapy and 6% of patients over the age of 3 years had hypogammaglobulinemia. We conclude that DiGeorge syndrome is associated with significant humoral immune deficiency.

IgA deficiency: clinical correlates with IgG subclass and mannan-binding lectin deficiencies.

OBJECTIVE: To characterize an IgA deficient population in terms of the incidence of IgG subclass and mannose-binding lectin (MBL) deficiencies and the type and severity of infections and other associated disorders. BACKGROUND: Selective IgA deficiency is probably the commonest of the primary immunodeficiency disorders and although it may lead to an increased risk for respiratory and gastrointestinal infections and associated to various autoimmune diseases, it may also be asymptomatic. Several studies have suggested the need of a concomitant defect in order for manifestation of its symptoms. METHODS: A total of 27 patients fulfilling the diagnostic criteria of selective IgA deficiency were evaluated for IgG subclass and MBL deficiencies after a thorough medical history, physical examination and pertinent evaluation for concomitant medical conditions. RESULTS: The overall incidence of IgG subclass deficiency found in the IgA deficient group was 18.5%. MBL deficiency was found to be 3.7%. These frequencies may have been influenced by the age group evaluated and the size of the population studied. Severe infections were more common in patients with combined deficiencies, either IgA and any of the IgG subclasses or IgA and MBL deficiency. Atopy was widely represented in the patients studied. CONCLUSIONS: The observed relationship between combined deficiencies Ig A, IgG subclasses and MBL and the increased representation of severe infections needs to be corroborated in a larger sample of patients with an inclusion of pediatric patients.

IgA deficiency: clinical correlates with IgG subclass and mannan-binding lectin deficiencies

OBJECTIVE: To characterize an IgA deficient population in terms of the incidence of IgG subclass and mannose-binding lectin (MBL) deficiencies and the type and severity of infections and other associated disorders. BACKGROUND: Selective IgA deficiency is probably the commonest of the primary immunodeficiency disorders and although it may lead to an increased risk for respiratory and gastrointestinal infections and associated to various autoimmune diseases, it may also be asymptomatic. Several studies have suggested the need of a concomitant defect in order for manifestation of its symptoms. METHODS: A total of 27 patients fulfilling the diagnostic criteria of selective IgA deficiency were evaluated for IgG subclass and MBL deficiencies after a thorough medical history, physical examination and pertinent evaluation for concomitant medical conditions. RESULTS: The overall incidence of IgG subclass deficiency found in the IgA deficient group was 18.5. MBL deficiency was found to be 3.7. These frequencies may have been influenced by the age group evaluated and the size of the population studied. Severe infections were more common in patients with combined deficiencies, either IgA and any of the IgG subclasses or IgA and MBL deficiency. Atopy was widely represented in the patients studied. CONCLUSIONS: The observed relationship between combined deficiencies Ig A, IgG subclasses and MBL and the increased representation of severe infections needs to be corroborated in a larger sample of patients with an inclusion of pediatric patients.

Prevalence of celiac disease in Brazilian children of short stature.

The aim of the present study was to determine the prevalence of celiac disease in children of short stature and to assess whether some of the routine laboratory examinations performed to determine the cause of short stature could suggest the presence of celiac disease. A total of 106 children of short stature and no gastrointestinal symptoms were studied. An extensive endocrine work-up had been negative for all of them and an additional investigation was performed by measuring the concentration of antiendomysial antibody. Patients who were positive for antiendomysial antibody (> or =1:10) or who exhibited IgA deficiency (less than 5 mg/dl) were referred for an endoscopic intestinal biopsy. We detected a pathological titer of antiendomysial IgA in six of these patients. Five of them showed histological abnormalities compatible with celiac disease and one had normal histology and was considered to have potential celiac disease. The prevalence of celiac disease in the population studied was 4.7% (with another 0.9% of the subjects being considered to have potential celiac disease). The children with celiac disease did not differ in any of the parameters tested when compared to those without celiac disease, though they showed an improvement in growth velocity after treatment with a gluten-free diet. We conclude that it is important to test all children with short stature for celiac disease by measuring antiendomysial IgA.

Deficiency of humoral immunity in cartilage-hair hypoplasia.

OBJECTIVE: Cartilage-hair hypoplasia (CHH), a metaphyseal chondrodysplasia, is usually associated with impaired cellular immunity. This study evaluates humoral immunity in patients with CHH. METHODS: The concentrations of immunoglobulins G, A, and M (IgG, IgA, and IgM) and IgG subclasses were studied in 20 patients. Data for 5 additional patients with recurrent infections were retrospectively reviewed. RESULTS: Seven of the prospectively evaluated patients (35%) had defective humoral immunity. Three patients had IgA deficiency. Four patients had IgG2 deficiency, accompanied by IgA deficiency, IgG4 deficiency, or both in 3 patients. IgG4 was low in most patients. Increased infections were usually associated with supranormal IgG and IgG1 and subnormal IgA, IgG2, or IgG4 concentrations. One retrospectively reviewed patient had severe hypogammaglobulinemia, and 3 had multiple IgG subclass deficiencies. CONCLUSIONS: Humoral immunity is impaired in CHH and contributes to the increased susceptibility to infections.

Celiac disease and selective immunoglobulin A deficiency.

Selective IgA deficiency was observed in 12 of 688 (1.7%) patients with celiac disease who were clinically undistinguishable from patients with celiac disease with normal IgA levels. This high prevalence of IgA deficiency in patients with celiac disease makes serum IgA assay advisable when screening for celiac disease is performed by measurement of antigliadin antibodies or anti-IgA endomysium antibodies. Similarly, subjects with IgA deficiency should be considered at risk of celiac disease.