Evidence for existence of coeliac disease autoantigens apart from tissue transglutaminase.
BACKGROUND
The pathogenesis of coeliac disease (CD) and of dermatitis herpetiformis (DH) is strongly associated with production of autoantibodies, defined by indirect immunohistology. Recently, tissue transglutaminase (tTG) was identified as a prominent autoantigen. It would be important to investigate 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 samples from patients with CD or DH. Double label experiments were performed using monoclonal as well as polyclonal tTG antibodies (anti-tTG) and patient sera. The staining was investigated by using conventional light and confocal laser scanning microscopy.


RESULTS
Most autoantibody binding sites were matched by tTG. Further, the binding of autoantibodies could be inhibited by preincubation with monoclonal anti-tTG. However, in nine serum samples (64%) autoantibody staining suggested a few distinct binding sites apart from tTG. In three sera (21 %) autoantibody binding fibres were detected which definitely did not match monoclonal anti-tTG signals. Distinctly stained fibres were confirmed by applying polyclonal anti-tTG. This indicates the existence of autoantigenic epitopes not related to tTG.
Uhlig
H H
HH
Department of Paediatrics, of the University Hospital, Leipzig, Germany.
Lichtenfeld
J
J
Osman
A A
AA
Richter
T
T
Mothes
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites; D002446:Celiac Disease / Q000276:immunology*; D003874:Dermatitis Herpetiformis / Q000276:immunology*; D005903:Gliadin / Q000276:immunology*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D007583:Jejunum / Q000276:immunology; D020527:Microscopy, Scanning Probe; D011817:Rabbits; D011503:Transglutaminases / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D005903:Gliadin; D011503:Transglutaminases