Abstract

Objective. Anti-tissue-transglutaminase-antibodies (anti-TG2) are the serological marker of celiac disease (CD). Given the close association between CD and type 1 diabetes, we investigated the production and deposition of anti-TG2-antibodies in the jejunal mucosa of type 1 diabetes children.

Research Design and Methods. Intestinal biopsies were taken from 33 type 1 diabetes patients with a normal mucosal architecture: 14 had high levels (potential-CD patients) and 19 had normal levels of serum anti-TG2. All biopsies were investigated for intestinal deposits of IgA anti-TG2 by double immunofluorescence. In addition, an antibody analysis using the phage display technique was carried out on the intestinal biopsies from seven type 1 diabetes patients, of which four had elevated and three had normal levels of serum anti-TG2.

Results. Immunofluorescence studies showed that 11/14 type 1 diabetes children with elevated levels and 11/19 with normal serum levels of anti-TG2 presented with mucosal deposits of such autoantibodies. The phage display analysis technique confirmed the intestinal production of the anti-TG2-antibodies; however, whereas the serum positive type 1 diabetes patients showed a preferential use of the VH5 antibody gene family, in the serum negative patients the anti-TG2-antibodies belonged to VH1 and VH3 families, with a preferential use of the latter.

Conclusions. Our findings demonstrate that there is intestinal production and deposition of anti-TG2-antibodies in the jejunal mucosa of the majority of type 1 diabetes patients. However, only those with elevated serum levels of anti-TG2-antibodies showed the VH usage that is typical of the anti-TG2-antibodies that are produced in CD patients.