IgA-Antigliadin Antibodies in Patients with IgA Nephropathy: The Secondary Phenomenon?

Abstract

Circulating IgA-antigliadin antibodies (IgA-AGA) are often found in patients with IgA nephropathy (NP). IgA-AGA are sensitive markers of an abnormal immune system reaction to gluten, seen particularly in patients with celiac disease. However, a lack of IgA-antireticulin and IgA-antiendomysium antibodies and often jejunal mucosal atrophy of patients with IgA NP suggest that most patients do not have latent celiac disease. To examine the relationship between IgA-AGA and clinical data, enzyme-linked immunosorbent assays for IgA-AGA were performed in 28 patients with IgA NP and in 50 healthy persons. The results were calculated in arbitrary units (AU). The cutoff level for a negative or a positive test was found to be 60 AU, calculated according to the AGA test result (mean + 3 SD) in 50 healthy persons. The following clinical data were assessed: age, gender, disease duration, daily proteinuria, blood pressure, serum creatinine, and creatinine clearance. Control sera were negative for IgA-AGA. Positive IgA-AGA tests were observed in 14 of the 28 patients (p < 0.0001 vs. controls) and high levels of IgA-AGA (AU >90) in 6 of the 28 patients (p < 0.001 vs. controls). The mean duration of the disease of the patients with positive IgA-AGA was significantly longer as compared with the patients who had a negative antibody test. IgA-AGA correlated with age (p < 0.05, r = 0.56), disease duration (p < 0.05, r = 0.40), and blood pressure (p < 0.05, r = 0.48). Antireticulin and antiendomysium antibody tests were negative in all patient and control sera. We conclude that IgA-AGA are associated with the progression of IgA NP. Our findings support the current concept about the pathogenesis of IgA NP, where the defective IgA production itself may be the primary and intestinal lesions as well as the production of IgA-AGA the secondary phenomenon.

O-Glycosylation of Serum IgA1 Antibodies against Mucosal and Systemic Antigens in IgA Nephropathy

“…The raised VV binding of total serum IgA1 in IgAN is probably a consequence of an increased proportion of circulating mucosal-type IgA1 antibodies in these patients. Our previous published study of this group of patients with IgAN showed that their serum levels of IgA1 anti-HP are higher than those of control subjects (18), and other groups have demonstrated the same for other mucosal antigens (38,39).…”

O-Glycosylation of Serum IgD in IgA Nephropathy

“…Circulating T cells display increased activation and cytokine production (31-36), and there is persistent systemic overproduction of pIgA1 against a variety of systemic and mucosal antigens (37)(38)(39), but this is associated with a failure of affinity maturation of serum IgA antibodies (40). In the mucosa, subclinical intestinal inflammation is found in IgAN (41,42), but mucosal pIgA1 plasma cell numbers (42,43) and mucosally secreted IgA antibody responses (44) are reduced.…”

Increased Prevalence of Anti-Gliadin IgA-Antibodies with Aberrant Duodenal Histopathological Findings in Patients with IgA-Nephropathy and Related Disorders

“…Ots et al (24) found elevated IgA-AGA in about 50% of the patients with IgAN, which in Ots' study was also correlated to age, disease duration and blood pressure. Contradictory findings have however been described by others.…”

“…Although several studies have shown an increased frequency of serologic markers of coeliac disease in IgA-nephropathy, the substantiation of a correlation between IgA nephropaty and verified celiac disease has been inadequate except for a recent study from Collin P et al (24,25). The evidence of a role for other food antigens has been debated but is still unclear (6).…”