Pathogenesis of autoimmune diseases: antibodies against transglutaminase, peptidylarginine deiminase and protein-bound citrulline in primary Sjögren's syndrome, multiple sclerosis and Alzheimer's disease.
Coeliac disease (CD) is becoming a model for understanding the pathogenesis of autoimmune disorders. In CD, antibodies against transglutaminase 2 (TG2) and specific residues of gliadins have been identified. A similar situation is seen in rheumatoid arthritis (RA) with both anti-citrullinated protein antibodies (ACPA) and auto-antibodies against the citrullinating enzyme, peptidylarginine deiminase (PAD). Previously, we have suggested that a complex between an enzyme and its modified substrate constitutes the neoantigen in autoimmune diseases. Our hypothesis is challenged by findings in patients of primary Sjögren's syndrome (pSS) who do not express ACPA, but who have been reported to carry anti-PAD. The aims of our investigation were to reproduce the study claiming the presence of anti-PAD in pSS and screen for ACPA and antibodies against TG2 and PAD in pSS (n = 78), multiple sclerosis (MS) (n = 85) and Alzheimer's disease (AD) (n = 79) using ELISA. With blood donors (n = 100) as controls, no increased occurrence of autoantibodies was found among the patient groups tested. Contrary to what has been published previously, patients with pSS do not express anti-PAD. The hypothesis of a complex between an enzyme and its modified substrate constituting the neoantigen in autoimmune diseases is still valid. The prevalence of anti-PAD, anti-TG2 and ACPA is comparatively restricted. PAD and TG2 do not seem to be involved directly in autoimmune mechanisms in pSS, MS or AD.
Bodil Roth
E
E
Hospital Pharmacy, Malmö University Hospital, Malmö, Sweden. bodil.roth@apoteket.se
Theander
E
E
Londos
E
E
Sandberg-Wollheim
M
M
Larsson
A
A
Sjöberg
K
K
Stenberg
P
P
D000544:Alzheimer Disease / Q000097:blood*; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000097:blood / Q000503:physiopathology*; D002956:Citrulline / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D019204:GTP-Binding Proteins / Q000276:immunology*; D006801:Humans; D006867:Hydrolases / Q000276:immunology*; D009103:Multiple Sclerosis / Q000097:blood*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D000076342:Protein-Arginine Deiminases; D011506:Proteins / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000097:blood*; D011503:Transglutaminases / Q000276:immunology*
D001323:Autoantibodies; D011506:Proteins; D002956:Citrulline; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases; D019204:GTP-Binding Proteins