Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-11-25
pubmed:abstractText
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.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1546-1718
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1319-24
pubmed:dateRevised
2010-10-4
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Specific interaction between genotype, smoking and autoimmunity to citrullinated alpha-enolase in the etiology of rheumatoid arthritis.
pubmed:affiliation
Rheumatology Unit, Karolinska Institutet, Center for Molecular Medicine, Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural