ASSOCIATIONS BETWEEN HLA-DRB1 SHARED EPITOPES ALLELES AND ANTI-RA33 ANTIBODIES IN DIFFERENT SUBSETS OF RHEUMATOID ARTHRITIS IN MALAYSIAN POPULATION

• The mechanisms affecting anti-RA33 antibody’s involvement in RA pathogenesis is still unclear. Refining our understanding of anti-RA33’s role in RA in relation to known RA-associated genes and serological elements is needed.Objectives:We investigated the relationship between RA-associated HLA-DRB1 epitope (SE) allele and presence of anti-RA33 antibodies in different serological subsets of rheumatoid arthritis in a Malaysian population.Methods:Serum samples from 550 RA cases comprising seronegative (negative for anti-CCP2, IgG and IgM, n=250), seropositive (triple-autoantibody positive, n=150), singular anti-CCP2 positive (n=100), and double RF positive RA (n=50) were chosen from the Malaysian Epidemiological Investigations of RA (MyEIRA) case-control study. Three hundred MyEIRA population controls were used for comparison. All serum samples were assayed using a commercial anti-RA33 ELISA kit. All genetic samples were genotyped for four-digit HLA-DRB1 alleles using the PCR-SSO method on Luminex platform.Results:The proportions of anti-RA33 positive was 20.9% in all RA cases (i.e. 34% in RF only positive RA; 25% in seropositive RA; 18% in seronegative RA and 18% in anti-CCP2 only positive RA). The HLA-DRB1 shared epitope alleles were significantly associated with anti-RA33 positive in the seropositive RA subgroup (OR=6.9, 95% CI 1.4-34.8; p=0.02). We observed significant association between anti-RA33 negative and HLA-DRB1 SE alleles among the seropositive RA patients (OR=4.5, 95% CI 2.8-7.2; p<0.001) and among CCP only positive RA (OR=4.4; 95% CI 2.6-7.4; p<0.01). No association was observed between anti-RA33 status and HLA-DRB1 SE alleles in seronegative RA and RF only positive RA.Conclusion:The HLA-DRB1 SE alleles increased the risk of seropositive and CCP only positive RA independent of anti-RA33 positivity.References:[1]Boeters, Debbie M et al. “The 2010 ACR/EULAR criteria are not sufficiently accurate in the early identification of autoantibody-negative rheumatoid arthritis: Results from the Leiden-EAC and ESPOIR cohorts.” Seminars in arthritis and rheumatism vol. 47,2 (2017): 170-174.[2]de Brito Rocha, Sara et al. “Clinical and pathophysiologic relevance of autoantibodies in rheumatoid arthritis.” Advances in rheumatology (London, England) vol. 59,1 2. 17 Jan. 2019.Acknowledgements:The authors would like to thank the Director General of Health, Ministry of Health Malaysia for supporting this study. The authors are also indebted to participants for their kind participation. This study was financially supported by the Ministry of Health, Malaysia (JPP-IMR 08-012).Disclosure of Interests:None declared

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