Selective IgA Deficiency

Abstract

IntroductionImmunoglobulin A (IgA) deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes. 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.IgA and Its FunctionsAlthough IgA is the most abundant antibody isotype produced in the body, its functions are not clearly understood. Subclass IgA1 in monomeric form is mainly found in the blood circulation, whereas subclass IgA2 in dimeric form is the dominant immunoglobulin in mucosal secretions. Secretory IgA appears to have prime importance in immune exclusion of pathogenic microorganisms and maintenance of intestinal homeostasis. Despite this critical role, there may be some compensatory mechanisms that would prevent disease manifestations in some IgA-deficient individuals.PathogenesisIn IgA deficiency, a maturation defect in B cells to produce IgA is commonly observed. Alterations in transmembrane activator and calcium modulator and cyclophilin ligand interactor gene appear to act as disease-modifying mutations in both IgA deficiency and common variable immunodeficiency, two diseases which probably lie in the same spectrum. Certain major histocompatibility complex haplotypes have been associated with susceptibility to IgA deficiency.ConclusionThe genetic basis of IgA deficiency remains to be clarified. Better understanding of the production and function of IgA is essential in elucidating the disease mechanism in IgA deficiency.

Proteobacteria-specific IgA regulates maturation of the intestinal microbiota

“…39 Of particular note, 10-15% of IgA deficient individuals are susceptible to inflammatory and autoimmune gastrointestinal disorders including Crohn disease and ulcerative colitis. 40 Mouse models of immunoglobulin deficient mice have shown altered transcriptome profiles, 26 indicating compensation by other immune mechanisms of defense. This may explain the mild baseline phenotype seen in IgA deficient mice but could also contribute to the enhanced susceptibility when challenged with DSS.…”

Current prospects and future challenges for nasal vaccine delivery

“…18 A small amount of IgA can be found in the serum while most of the IgA is located in external secretions known as secretory IgA (sIgA). 24 IgA consist of a dimer or tetramer, a joining J-chain polypeptide and a polypeptide chain called the secretory component. 24,25 IgA has several functions in mucosal defense including the entrapment of antigens or pathogens in mucus to prevent them from direct contact with the mucosal surface.…”

“…24 IgA consist of a dimer or tetramer, a joining J-chain polypeptide and a polypeptide chain called the secretory component. 24,25 IgA has several functions in mucosal defense including the entrapment of antigens or pathogens in mucus to prevent them from direct contact with the mucosal surface. 15,26 In addition, sIgA may also block or provide steric hindrance to surfaces of pathogenic molecules that may inhibit their attachment to the epithelium.…”

Immunoglobulin A and its selective deficiency

“…контролирующих переключение синтеза Ig, что приводит к нарушению последнего этапа со-зревания и дифференцировки В-лимфоцитов в плазматичес кие IgA-секретирующие клетки [17]. Обсуждались и другие механизмы: дефекты или нарушение функциональной активности Т-хелперов, снижение экспрессии рецептора CD40 на В-лимфоцитах, избыточная активность регуляторных Т-клеток, низкий уровень интер-лейкинов-4, -6, -7, -10 и -21, Т-клеточного росто-вого фактора β [7,17,18].…”