The role of the immune response against tissue transglutaminase in the pathogenesis of coeliac disease.
The development of autoimmunity to tissue transglutaminase (TGase 2) is a striking feature of coeliac disease, an enteropathy that develops in genetically susceptible individuals upon exposure to dietary gluten. IgA anti-TGase 2 autoantibodies are present in at least 98% of coeliac patients on a gluten-containing diet and provide a valuable tool for the diagnosis of the disorder. During disease development, the formation of TGase 2-gliadin complexes through TGase 2 activity appears to be central for B-cell epitope spreading from gliadin to TGase 2. However, the potential role of an immune response against TGase 2 in the pathogenesis of coeliac disease and for the development of the intestinal lesion remains unclear. Recently, an inhibitory effect of anti-TGase 2 autoantibodies from coeliac patients on TGase 2 activity in vitro has been described. Here, we report that a cellular and humoral response against TGase 2 can be induced in TGase 2 (-/-) and wildtype mice on a C57BL/6 background by s.c. immunization with human recombinant or guinea pig TGase 2 in complete Freund's adjuvant. Immunized wildtype, but not TGase 2 (-/-) mice develop periductal lymphocytic infiltrates in lacrimal glands. Although no intestinal lesions were found, this observation lends support to the concept that the development of autoimmunity against TGase 2 is a pathological event that might ultimately lead to organ damage.
Freitag
Tobias
T
Medical Department I, University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany. tobias.freitag@med1.imed.uni-erlangen.de
Schulze-Koops
Hendrik
H
Niedobitek
Gerald
G
Melino
Gerry
G
Schuppan
Detlef
D
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D002446:Celiac Disease / Q000209:etiology / Q000276:immunology*; D019204:GTP-Binding Proteins / Q000276:immunology*; D006801:Humans; D007765:Lacrimal Apparatus / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology*
D001323:Autoantibodies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins