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- Title
Specific interaction between genotype, smoking and autoimmunity to citrullinated alpha-enolase in the etiology of rheumatoid arthritis.
- Authors
Mahdi, Hiba; Fisher, Benjamin A; Källberg, Henrik; Plant, Darren; Malmström, Vivianne; Rönnelid, Johan; Charles, Peter; Ding, Bo; Alfredsson, Lars; Padyukov, Leonid; Symmons, Deborah P M; Venables, Patrick J; Klareskog, Lars; Lundberg, Karin
- Abstract
Gene-environment associations are important in rheumatoid arthritis (RA) susceptibility, with an association existing between smoking, HLA- DRB1 'shared epitope' alleles, PTPN22 and antibodies to cyclic citrullinated peptides (CCP). Here, we test the hypothesis that a subset of the anti-CCP response, with specific autoimmunity to citrullinated alpha-enolase, accounts for an important portion of these associations. In 1,497 individuals from three RA cohorts, antibodies to the immunodominant citrullinated alpha-enolase CEP-1 epitope were detected in 43-63% of the anti-CCP-positive individuals, and this subset was preferentially linked to HLA-DRB1*04. In a case-control analysis of 1,000 affected individuals and 872 controls, the combined effect of shared epitope, PTPN22 and smoking showed the strongest association with the anti-CEP-1-positive subset (odds ratio (OR) of 37, compared to an OR of 2 for the corresponding anti-CEP-1-negative, anti-CCP-positive subset). We conclude that citrullinated alpha-enolase is a specific citrullinated autoantigen that links smoking to genetic risk factors in the development of RA.
- Publication
Nature genetics, 2009, Vol 41, Issue 12, p1319
- ISSN
1546-1718
- Publication type
Journal Article
- DOI
10.1038/ng.480