Journal
RHEUMATOLOGY
Volume 49, Issue 12, Pages 2298-2304Publisher
OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/keq273
Keywords
Rheumatoid arthritis; Anti-citrullinated peptide antibody; HLA; Shared epitope; Subset; Genetics; Association study
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Funding
- Ministry of Health, Labor and Welfare of Japan
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Japan Rheumatism Foundation
- Waksman Foundation
- Mitsubishi Pharma Research Foundation
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Methods. We genotyped HLA-DRB1 alleles for 574 ACPA-positive RA, 185 ACPA-negative RA (including 97 erosive RA) and 1508 healthy donors. We also tested whether HLA-DR SE is associated with RF-negative or ANA-negative RA. Results. ACPA-negative RA with apparent bone erosion was not associated with SE, supporting the idea that ACPA-negative RA is genetically distinct from ACPA-positive RA. We also tested whether these subsets are based on autoantibody-producing activity. In accordance with the ACPA-negative RA subset, the RF-negative RA subset showed a clearly distinct pattern of association with SE from the RF-positive RA. In contrast, ANA-negative as well as ANA-positive RA was similarly associated with SE, suggesting that the subsets distinguished by ACPA are not based simply on differences in autoantibody production. Conclusions. ACPA-negative erosive RA is genetically distinct from ACPA-positive RA.
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