Abstract
IntroductionThe purpose of this study was to investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF).MethodsWe studied 408 patients (235 with RA, 173 non-RA) and 269 controls. ACPA, RF and HLA-DR typing were determined.ResultsWe found an increased frequency of HLA DRB1 alleles with the shared epitope (SE) in ACPA-positive RA. Inversely, HLA DRB1 alleles encoding DERAA sequences were more frequent in controls than in ACPA-positive RA, and a similar trend was found for HLA DR3. However, these results could not be confirmed after stratification for the presence of the SE, probably due to the relatively low number of patients. These data may suggest that the presence of these alleles may confer a protective role for ACPA-positive RA. In RA patients we observed association between SE alleles and ACPA titers in a dose-dependent effect. The presence of HLA DR3 or DERAA-encoding alleles was associated with markedly reduced ACPA levels. No association between RF titers and HLA DR3 or DERAA-encoding alleles was found.ConclusionsHLA DRB1 alleles with the SE are associated with production of ACPA. DERAA-encoding HLA-DR alleles and HLA DR3 may be protective for ACPA-positive RA.
Highlights
The purpose of this study was to investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF)
We found a higher frequency of shared epitope (SE) alleles in anti-citrullinated protein antibody (ACPA)-positive RA compared with healthy controls (67.8% versus 41.6%, odds ratio (OR) 2.95, confidence interval (CI) 1.93 to 4.53, P < 0.001), but we did not observe this relationship with ACPA-negative RA patients and controls (35.2% versus 41.6%, P = 0.31), indicating that SE alleles are associated with ACPA production in RA
The presence of HLA-DR3 or DERAA-encoding alleles was associated with markedly reduced ACPA levels
Summary
The purpose of this study was to investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF). Rheumatoid arthritis (RA) is a complex autoimmune disease that develops from the combined effects of genetic and environmental factors. Anti-citrullinated protein antibodies (ACPAs) seem to play a pivotal role in the pathogenesis of RA as they are highly specific [6], can be detected years before the onset of symptoms [7,8], may predict progression to RA in patients with undifferentiated arthritis [9,10], are associated with the extent of joint destruction [11], and enhance disease severity in animal models of arthritis [12]
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