Association of human leukocyte antigen-DRB1 with anti-cyclic citrullinated peptide autoantibodies in Saudi patients with rheumatoid arthritis

BACKGROUND: The genetic association between human leukocyte antigen (HLA)-DRB1 alleles and the risk of development of autoantibodies has been investigated, but there are few studies from the Gulf region. OBJECTIVES: To investigate the association between the HLA-DRB1 shared epitope and the risk for development of autoantibodies in rheumatoid arthritis (RA) patients in a Saudi population. DESIGN: Analytical cross-sectional study. SETTING: Tertiary care hospital in Riyadh, Saudi Arabia. PATIENTS AND METHODS: We enrolled consecutive Saudi RA patients attending the rheumatology clinic between January and April 2015. Previously published data on HLA typing on unmatched healthy controls were used for comparison. HLA typing was performed using sequence-specific oligonucleotide probes (SSOP). Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and antinuclear antibodies (ANA) were also measured. Logistic regression analysis was used to study the autoantibodies as possible explanatory variables for the presence of the HLA-DRB1 shared epitope. MAIN OUTCOME MEASURE(S): The association between the presence of the shared epitope and the risk of developing anti-CCP antibodies, ANA, and RF. RESULTS: In 76 patients with RA, carrying the shared epitope was associated with a significantly higher risk of having RA [OR=2.65, 95% CI (1.42–4.94), P=.0009]. However, only HLA-DRB1*04:05 was significantly associated with RA [OR=3.73, 95% CI (1.61–8.96), Pc=.016]. In the logistic regression analysis, only anti-CCP was significantly associated with the shared epitope [OR=14.51, 95% CI (1.53–137.49), P=.02]. CONCLUSIONS: Our analysis indicates that the presence of the HLA-DRB1 shared epitope is strongly associated with the development of anti-CCP antibodies in Saudi patients with RA. LIMITATIONS: A larger sample size is needed to confirm our finding.