IgA cross-reactivity between a nuclear autoantigen and wheat proteins suggests molecular mimicry as a possible pathomechanism in celiac disease

Celiac disease patients display IgA antibody reactivity to wheat as well as to human proteins. We used serum IgA from celiac patients and, for control purposes, from patients with Crohn's disease, ulcerative colitis and from healthy individuals to identify celiac disease-specific IgA autoantigens in nitrocellulose-blotted extracts from various human cell types (epithelial, endothelial, intestinal cells, fibroblasts). The pattern, recognition inte nsity and time course of IgA autoreactivity was monitored using serial seru m samples obtained from celiac children before and under gluten-free diet. By immunoblot inhibition and subcellular (cytosolic, nuclear) cell fraction ation we identified a 55 kDa nuclear autoantigen expressed in intestinal, e ndothelial cells and in fibroblasts which was recognized by IgA antibodies of approximately half of the celiac disease patients and cross-reacted with wheat proteins. IgA reactivity to the 55 kDa autoantigen disappeared durin g gluten-free diet and was inhibited after pre-absorption of sera with whea t proteins but not with tissue transglutaminase, previously reported as the unique celiac disease-specific autoantigen. In conclusion, we defined a no vel 55 kDa celiac disease-specific nuclear IgA autoantigen which shares epi topes with wheat proteins and which is different from tissue transglutamina se and calreticulin. Although the newly defined autoantigen was recognized much less frequently than tissue transglutaminase, our data suggest molecul ar mimicry between wheat and human proteins as a possible pathomechanism fo r the induction and/or maintenance of mucosal tissue damage in celiac disea se.