Secretory immunoglobulin A (IgA) responses in IgA nephropathy patients after mucosal immunization, as part of a polymeric IgA response

Abstract

SummarySecretory immunoglobulin A (SIgA), although generated at mucosal surfaces, is also found in low concentrations in the circulation. Recently, SIgA was demonstrated in mesangial deposits of patients with immunoglobulin A nephropathy (IgAN), suggesting a role in the pathogenesis. This finding is in line with the belief that high molecular weight (HMW) immunoglobulin A (IgA) is deposited in the kidney. However, there is little information on the size distribution of antigen-specific IgA in circulation upon mucosal challenge. In this study we measured antigen-specific IgA, including SIgA, in serum following challenge of IgAN patients and controls via intranasal vaccination with a neoantigen, cholera toxin subunit B (CTB). We sizefractionated serum and nasal washes to study the size distribution of total IgA, SIgA and CTB-specific IgA. Finally, we compared the size distribution of antigen-specific IgA after mucosal immunization with the distribution upon systemic immunization. A significant induction of antigen-specific SIgA was detectable in serum of both patients with IgAN and controls after mucosal immunization with CTB. Independent of the route of immunization, in both groups the antigen-specific IgA response was predominantly in the polymeric IgA fractions. This is in contrast to total IgA levels in serum that are predominantly monomeric. We conclude that mucosal challenge results in antigenspecific SIgA in the circulation, and that the antigen-specific IgA response in both IgAN patients and in controls is of predominantly HMW in nature. No differences between IgAN patients and controls were detected, suggesting that the size distribution of antigen-specific IgA in the circulation is not disturbed specifically in IgAN patients.

Proliferation and Cytokine Production of Human Mesangial Cells Stimulated by Secretory IgA Isolated from Patients with IgA Nephropathy

“…The level of SIgA in saliva provides much information about the functional status of the entire mucosal immune system [34]. In addition, its concentration in saliva is high (∼ 35-81 μg/ml) but low in serum (∼9-18 μg/ml) in adults [6,34,35,36]. Moreover, previous studies have shown underglycosylated IgA molecules produced by tonsils could be one origin of glomerular IgA in patients with IgAN [33,37,38].…”

The Origin and Activities of IgA1-Containing Immune Complexes in IgA Nephropathy

“…systemic antigens ( 120 ). Moreover, some investigators have found secretory IgA1 (with secretory component) in renal deposits ( 123 , 124 ) or polymeric IgA1 ( 125 ), suggesting that this IgA1 was generated during a mucosal immune response ( 126 ). It is not clear whether secretory IgA1, regardless of its O -glycosylation pattern, may be a major driver of the pathogenesis of IgAN.…”

Circulating secretory IgA antibodies against cyclic citrullinated peptides in early rheumatoid arthritis associate with inflammatory activity and smoking

“…In contrast to circulating IgA, which is mostly monomeric, SIgA is mainly dimeric and complexed with a secretory component (SC) (i.e., a remnant of the polymeric immunoglobulin receptor responsible for the active transport of antibodies across mucosal membranes) [ 27 ]. Eijgenraam et al reported antigen-specific SIgA in serum after mucosal immunization with cholera toxin subunit B [ 28 ]. Thus, mucosal immunization in autoimmune diseases could potentially be investigated by analysis of SIgA autoantibodies in serum, enabling more convenient sample handling, more reliable quantitative analyses, and access to larger patient cohorts compared with what is achievable regarding mucosal secretions.…”