Selective IgA Deficiency in Autoimmune Diseases

Abstract

SUMMARY

A utoimmune diseases occur when there is interruption of the usual control process, thereby allowing the immune system to malfunction and attack healthy cells and tissues. It usually involves both T-cell and B-cell responses. It only requires that the adaptive immune response be directed to a self-antigen and this is triggered by many factors e.g; genetic, environmental including infectious and noninfectious factors and loss of self-tolerance (Davidson and Diamond, 2001). According to the clinical manifestation, autoimmune diseases may be classified as systemic (e.g. systemic lupus erythematosus, or SLE) or as organ-specific (e.g. Graves’ disease). However, this clinically useful classification does not correspond to the underlying pathogenetic mechanisms. A multifactorial genesis, including immunological, genetic, endocrine, and environmental factors, is suggested by evidence from both human and animal studies (Shoenfeld and Isenberg, 1990). Selective IgA deficiency (sIgAD) is defined as the selective deficiency of serum immunoglobulin A (IgA) (ie, serum levels of immunoglobulin G [IgG] and immunoglobulin M [IgM] are normal) in a patient older than four years of age in whom other causes of hypogammaglobulinemia have been excluded (Yel, 2010). The aim of this study was to investigate the prevelance of Selective immunoglobulin A deficiency in patients with autoimmune diseases and highlighting its possible pathophysiological mechanisms. This study was a case control study conducted on one hundred patients diagnosed to have an autoimmune disease ranging from 20 to 60 years of age attending the Ain Shams University clinic and twenty healthy individuals age and sex matched as control group. All participants were subjected to full history and clinical examination of the autoimmune disease, serum immunoglobulin A by (ELISA), routine laboratory & radiological investigations to exclude organ failure that may affect the study. Data was collected regarding gender, age, clinical history and specific investigations. Patients who were on current medications that may affect the results of the study, with organ failure, severely ill, pregnant females or patients with concomitant diseases that may affect the results of the study were excluded. In our study we found statistically highly significant evidence of selective IgA deficiency among cases having different autoimmune diseases included in our study regarding age, sex, type of autoimmune disease and duration of illness. 67% of the patients were found to have IgA deficiency and all of the control had normal IgA levels. The frequency of different autoimmune diseases involved in our study revealed high frequency of type1 diabetes mellitus (T1DM) 20%, Rheumatoid Arthritis (RA) 17%, Systemic lupus erythematosus (SLE) 14%, Autoimmune hemolytic anemia (AIHA) 13%, Autoimmune thyroiditis 12%, Idiopathic thrombocytopenic purpura (ITP) 11% on the other hand low frequency of crohn,s disease 1%, ulcerative colitis 2%, Autoimmune hepatitis 2%, Grave,s disease 2%, celiac disease 3%, Antiphospholipid syndrome (APL$) 3%. We also found variation in IgA level between different types of autoimmune diseases included in the study which was statistically significant but we couldnot determine the higher incidence in which autoimmune disease due to insufficient number of some autoimmune diseases and not all autoimmune diseases included in our study. The correlation between IgA level and age was statistically highly significant with inverse relationship between age and serum IgA level in patients included in our study on the other hand no correlation between IgA level and neither duration of illness or gender. Most individuals with IgA deficiency are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations (Yel, 2010). The increased infections in cohorts of IgAD might be the link to increased autoimmunity. Theories for this assume a breakdown of tolerance as a result of exposure of hidden or sequestrated antigens, molecular mimicry, and presence of superantigens or antigen drift because of a cytokine environment favouring bystander activation of B cells. Additional mechanisms that might permit autoimmune T- and B-cell reactive clones to persist are failure of apoptosis of self-reactive clones, cytokine dysregulation or failure of T-cell regulation (Samarkos and Vaipoulos, 2005 and Lopes-da-Silva and Rizzo, 2008).