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Specific interaction between genotype, smoking and autoimmunity to citrullinated alpha-enolase in the etiology of rheumatoid arthritis
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2009 (English)In: Nature Genetics, ISSN 1061-4036, Vol. 41, no 12, 1319-1324 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 41, no 12, 1319-1324 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-124910DOI: 10.1038/ng.480ISI: 000272144900014OAI: oai:DiVA.org:uu-124910DiVA: diva2:318131
Available from: 2010-05-06 Created: 2010-05-06 Last updated: 2010-09-21Bibliographically approved

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Rönnelid, Johan
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