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Specific interactio...
Specific interaction between genotype, smoking and autoimmunity to citrullinated alpha-enolase in the etiology of rheumatoid arthritis
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- Mahdi, H (author)
- Karolinska Institutet
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Fisher, BA (author)
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Källberg, H (author)
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Plant, D (author)
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- Malmström, V (author)
- Karolinska Institutet
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- Rönnelid, Johan (author)
- Uppsala universitet,Enheten för klinisk immunologi,Johan Rönnelid
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Charles, P (author)
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- Ding, B (author)
- Karolinska Institutet
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- Alfredsson, L (author)
- Karolinska Institutet
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- Padyukov, L (author)
- Karolinska Institutet
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Symmons, DP (author)
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Venables, PJ (author)
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- Klareskog, L (author)
- Karolinska Institutet
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Lundberg, K (author)
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(creator_code:org_t)
- 2009-11-08
- 2009
- English.
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:12, s. 1319-1324
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Mahdi, H
-
Fisher, BA
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Källberg, H
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Plant, D
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Malmström, V
-
Rönnelid, Johan
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show more...
-
Charles, P
-
Ding, B
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Alfredsson, L
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Padyukov, L
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Symmons, DP
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Venables, PJ
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Klareskog, L
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Lundberg, K
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show less...
- Articles in the publication
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Nature Genetics
- By the university
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Uppsala University
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Karolinska Institutet