Transglutaminase-independent binding of gliadin to intestinal brush border membrane and GM1 ganglioside.
Anti-ganglioside antibodies have been described in celiac disease or gluten sensitivity, in conjunction with the presence of central and peripheral nervous system deficits. The observed antibody reactivity to gangliosides is postulated to be related to the anti-gliadin immune response, either through antigenic mimicry, or by formation of gliadin-ganglioside complexes and haptenization. We examined the possibility of the presence of ganglioside-like epitopes in gliadin, as well as the potential for complex formation between gliadin and GM1 ganglioside. Low levels of glycosylation were present in gliadin, but ganglioside-like carbohydrate epitopes were not detected. However, gliadin was found to bind to GM1 ganglioside and to the GM1-rich intestinal brush border membrane. The described complex formation and possible haptenization of GM1 by gliadin may be responsible for driving the anti-ganglioside antibody response in some patients with gluten sensitivity. Furthermore, binding of gliadin to GM1 on the intestinal epithelium might have a role in the anti-gliadin immune response and contribute to the intestinal inflammatory reaction in celiac disease.
Alaedini
Armin
A
Department of Neurology and Neuroscience, 1300 York Ave, Weill Medical College of Cornell University, New York, NY 10021, USA. ara2004@med.cornell.edu
Latov
Norman
N
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology; D001342:Autonomic Nervous System Diseases / Q000276:immunology; D002446:Celiac Disease / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D017615:Enteric Nervous System / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005677:G(M1) Ganglioside / Q000276:immunology* / Q000378:metabolism; D005903:Gliadin / Q000276:immunology* / Q000378:metabolism; D006031:Glycosylation; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D046911:Macromolecular Substances / Q000276:immunology; D051379:Mice; D008871:Microvilli / Q000276:immunology*; D018716:Molecular Mimicry / Q000276:immunology; D010523:Peripheral Nervous System Diseases / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011503:Transglutaminases / Q000276:immunology
D001323:Autoantibodies; D000939:Epitopes; D046911:Macromolecular Substances; D005677:G(M1) Ganglioside; D005903:Gliadin; D011503:Transglutaminases; C105804:transglutaminase 1