Evidence for existence of coeliac disease autoantigens apart from tissue transglutaminase

Background The pathogenesis of coeliac disease (CD) and of dermatitis herpe tiformis (DH) is strongly associated with production of autoantibodies, def ined by indirect immunohistology. Recently, tissue transglutaminase (tTG) w as identified as a prominent autoantigen. It would be important to investig ate if further molecules apart from tTG are involved in autoimmunity. Methods Tissue sections of human foetal intestine were used to compare the distribution of tTG with the autoantibody binding patterns of 14 sera sampl es from patients with CD or DH. Double label experiments were performed usi ng monoclonal as well as polyclonal tTG antibodies (anti-tTG) and patient s era, The staining was investigated by using conventional light and confocal laser scanning microscopy, Results Most autoantibody binding sites were matched by tTG. Further, the b inding of autoantibodies could be inhibited by preincubation with monoclona l anti-tTG. However, in nine serum samples (64%) autoantibody staining sugg ested a few distinct binding sites apart from tTG, In three sera (21 %) aut oantibody binding fibres were detected which definitely did not match monoc lonal anti-tTG signals, Distinctly stained fibres were confirmed by applyin g polyclonal anti-tTG, This indicates the existence of autoantigenic epitop es not related to tTG. (C) 2000 Lippincott Williams & Wilkins.