Identification of celiac disease associated IgA nephropathy by IgA anti-tissue transglutaminase2 antibody deposits in archived formalin-fixed tissues.

Abstract

The causal association between IgA nephropathy (IgAN) and celiac disease (CeD) is based on their clinical coexistence. In this prospective study, we screened patients with IgAN for CeD and explored the utility of analysis of IgA anti-TG2 antibody deposits, for establishing a causal association. Biopsy-proven patients of IgAN were screened for serum IgA anti-tissue transglutaminase antibody (IgA anti-tTG Ab) titer and thereafter were invited to undergo endoscopic duodenal biopsy. Corresponding duodenal and kidney biopsies were subjected to IgA anti-TG2 antibody colocalization study using dual-color immunohistochemistry and immunofluorescence techniques. Additionally, kidney biopsies from 105 patients with IgAN who did not give consent for serology analysis, 30 non-IgA nephropathies, and 10 normal controls were also included. Dual-color-stained slides were interpreted based on stain distribution and intensity scores, and Pearson's index >0.3-1 on confocal imaging was considered significant. Of a cohort of 151 patients with IgAN, 32 consented to undergo sero-screening and 5 of them had high serum anti-tTG Ab titer. Two out of the latter consented to endoscopic duodenal biopsies, in whom modified Marsh grade 3b changes were identified. Strong IgA anti-TG2 antibody deposits were noted in the kidney and duodenal biopsies of these patients. One patient out of non-consenting 105 patients with IgAN and 3 out of 30 patients with other non-IgA nephropathies also showed IgA anti-TG2 deposits. None of the healthy kidney tissues showed IgA anti-TG2 Ab deposits. Co-localized IgA anti-TG2 deposits in the kidney biopsies in patients with IgAN help to establish a pathogenic link with CeD. A small proportion of patients with IgAN have associated CeD.