Dr. Liang has received consulting fees, speaking fees, and/or honoraria from Roche, Amgen/Wyeth, Bristol-Myers Squibb, Pfizer, and Abbott (less than $10,000 each) and owns stock or stock options in Merck Frosst.
Rheumatoid Arthritis Basic Science Studies
The DERAA HLA–DR alleles in patients with early polyarthritis: Protection against severe disease and lack of association with rheumatoid arthritis autoantibodies†
Article first published online: 26 FEB 2009
Copyright © 2009 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 60, Issue 3, pages 698–707, March 2009
How to Cite
Carrier, N., Cossette, P., Daniel, C., de Brum-Fernandes, A., Liang, P., Ménard, H. A. and Boire, G. (2009), The DERAA HLA–DR alleles in patients with early polyarthritis: Protection against severe disease and lack of association with rheumatoid arthritis autoantibodies. Arthritis & Rheumatism, 60: 698–707. doi: 10.1002/art.24353
ClinicalTrials.gov identifier: NCT00512239.
- Issue published online: 26 FEB 2009
- Article first published online: 26 FEB 2009
- Manuscript Accepted: 25 NOV 2008
- Manuscript Received: 30 JUN 2008
- The Arthritis Society. Grant Numbers: 00/0201, RG06/108
- Graduate Student award from the Canadian Arthritis Network
- Clinician Teacher award from The Arthritis Society
- Centre de Recherche Clinique Étienne-LeBel
- Fonds de la Recherche en Santé du Québec
To define the association of alleles encoding the HLA–DR rheumatoid arthritis (RA) protective epitope (DERAA) with the presence of RA-associated antibodies at study inclusion and with severe outcome in patients with early polyarthritis (EPA).
Consecutive EPA patients (n = 210) were evaluated early (mean of 4.8 months after diagnosis) and prospectively (for 30 months). HLA class II typing was performed by polymerase chain reaction using sequence-specific primers, and HLA–DR alleles DERAA, RA-associated shared epitope (SE), and non-SE/non-DERAA (neither SE nor DERAA) were identified. RA-associated antibodies identified were anti-Sa/citrullinated vimentin, anti–cyclic citrullinated peptide 2, and IgM rheumatoid factor. Severe disease was defined according to a preset threshold of joint destruction and/or functional limitation.
DERAA and SE alleles were present in 62 and 110 of the 210 EPA patients, respectively. At 30 months, severe disease was present in 78 patients (37%). In contrast to SE alleles, DERAA alleles were not associated with the production of RA-associated antibodies, but were strongly protective against severe disease at 30 months (odds ratio 0.30, P < 0.001). DERAA alleles emerged as a strong, independent protective marker on multivariate analysis. The protective effect of DERAA was seen only in patients who did not already have erosions at study inclusion, was independent of the presence of antibodies, but was not associated with spontaneous remission.
In our EPA cohort, the presence of a DERAA sequence was a strong independent predictor of a better prognosis, but only in the absence of erosive disease that was already present at inclusion. Identification of DERAA alleles may help in managing the large subgroup of EPA patients who do not have erosions at baseline.