RESEARCH - DERAA HLA-DR alleles in patients with early polyarthritis

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Arthritis Rheum. 2009 Feb 26;60(3):698-707.

The DERAA HLA-DR alleles in patients with early polyarthritis:

Protection against severe disease and lack of association with

rheumatoid arthritis autoantibodies.

r N, Cossette P, C, de Brum-Fernandes A, Liang P, Ménard

HA, Boire G.

Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada.

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.

CONCLUSION: 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.

PMID: 19248090

http://www.ncbi.nlm.nih.gov/pubmed/19248090

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