The DERAA HLA-DR alleles in patients with early polyarthritis: protection against severe disease and lack of association with rheumatoid arthritis autoantibodies.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Carrier
Nathalie
N
Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada.
Cossette
Pierre
P
Daniel
Claude
C
de Brum-Fernandes
Artur
A
Liang
Patrick
P
Ménard
Henri A
HA
Boire
Gilles
G
D000328:Adult; D000368:Aged; D000483:Alleles; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001168:Arthritis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D015331:Cohort Studies; D018450:Disease Progression; D000939:Epitopes / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010456:Peptides, Cyclic / Q000276:immunology; D011379:Prognosis; D012217:Rheumatoid Factor / Q000276:immunology; D012720:Severity of Illness Index; D014746:Vimentin / Q000276:immunology
D018501:Antirheumatic Agents; D001323:Autoantibodies; D000939:Epitopes; D006684:HLA-DR Antigens; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor