Transglutaminase and peptidylarginine deiminase in the pathogenesis of autoimmune diseases

Coeliac disease (CD) is becoming a model for understanding the pathogenesis of autoimmune disorders. In CD, antibodies against transglutaminase 2 (TG2) and specific glutamine residues of gliadins have been identified. A similar situation is seen in rheumatoid arthritis with both anticitrullinated 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. However, this hypothesis is challenged by findings in cases of primary Sjögren’s syndrome (pSS), who do not express ACPA, but who have been reported to carry anti-PAD. Objectives: Reproducing the study claiming the presence of anti-PAD in pSS. Screening for ACPA and antibodies against TG2 and PAD in pSS (n=78), multiple sclerosis (MS) (n=85), and Alzheimer’s disease (AD) (n=79). Methods: ELISAs. Results: With blood donors (n=100) as controls, no increased prevalence of autoantibodies was found among the patient groups tested. Conclusions: 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. Although attractive from a theoretical point of view, PAD and TG2 do not seem to be involved directly in autoimmune mechanisms in pSS, MS or AD.

Grantor dc:publisher

Chronic Inflammatory and Degenerative Diseases Research Unit

Year dc:date

2008

Author dc:creator

• Roth, Bodil

• Medical and Health Sciences
• multiple sclerosis
• pathogenesis
• peptidylargininedeiminase
• transglutaminase.
• Sjögren’s syndrome
• autoimmune
• Alzheimer’s disease

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

urn:isbn:978-91-85897-62-9

OAI identifier oai:identifier

oai:lup.lub.lu.se:1fb5b4b6-837b-406f-bd28-8ab80d8fd6fc