AB0697 IMPACT OF HLA-DRB1 SHARED EPITOPE, SMOKING AND ACPAS ON EROSIVE RHEUMATOID ARTHRITIS IN GREEK PATIENTS
Authors: E. N. Mole, A. Tarassi, A. Tzioufas, M. N. Manoussakis, A. Tsirogianni, S. Gazi, P. G. Vlachoyiannopoulos
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a complex, multifactorial autoimmune disease, whose aetiopathogenesis involves genetic and environmental factors. It remains unclear if these factors influence the radiographic damage in RA patients. <h3>Objectives:</h3> In this study we aimed to assess the main effects of shared epitope (SE) alleles, smoking and anti-citrullinated protein antibodies (ACPAs), as well as the possible interaction between them on the presence of erosive changes in hands and feet of 300 Greek patients with longstanding RA. <h3>Methods:</h3> The study comprised of 300 Greek RA patients. Current and past smokers were classified as smokers and those who had never smoked were classified as non-smokers. ACPA antibodies were determined by an enzyme-linked immunosorbent assay (ELISA) using commercial kits. An antibody titer ≥25IU was considered as positive. The HLA-DRB1 high-resolution typing was performed by molecular techniques: polymerase chain reaction and hybridization with sequence-specific oligonucleotide probes and/or specific primers (PCR-SSOP, PCR-SSP). X-rays were scored using modified Sharp/van der Heijde score and erosive disease was defined as the presence of at least one erosion on radiographs. Odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for sex, age, disease duration at inclusion were calculated by logistic regression analysis and p values less than 0.05 were considered as statistically significant. The Statistical Package for the Social Sciences, version 25 (IBM SPSS statistics) was used. <h3>Results:</h3> In total, 50% were smokers, 74.3% were women, 57.7% were ACPA positive, 62.7% possessed at least one copy of HLA-DRB1 SE allele and 56.7% had at least one erosion on radiographs. Erosive disease was significantly associated with presence of ACPAs (OR: 3.4 [95% CI 1.9-5.8], p&lt;0.001) and HLA-DRB1 SE (OR: 8.3 [95% CI 4.6-15.1], p&lt;0.001). Whereas, smoking didn't confer to erosive disease occurrence (OR: 1.3 [95% CI 0.7-2], p=0.4). Furthermore, we observed an interaction between smoking, HLA-DRB1 SE alleles and ACPAs in respect to erosive RA (OR: 15.06 [95% CI 5.7-39.7], p&lt;0.001, p&lt;0.001 for interaction). <h3>Conclusion:</h3> We identified that presence of SE and ACPAs increased the risk of developing erosive disease, while smoking didn't. Whereas, their interaction resulted in a significantly increased incidence of erosive RA. <h3>REFERENCES:</h3> [1] Finckh A, Dehler S, Costenbader KH, Gabay C; Swiss Clinical Quality Management project for RA. Cigarette smoking and radiographic progression in rheumatoid arthritis. Ann Rheum Dis. 2007 Aug;66(8):1066-71. doi: 10.1136/ard.2006.065060. Epub 2007 Jan 19. PMID: 17237117; PMCID: PMC1954718. [2] Takeuchi T, Soen S, Ishiguro N, Yamanaka H, Tanaka S, Kobayashi M, Okubo N, Nitta T, Tanaka Y. Predictors of new bone erosion in rheumatoid arthritis patients receiving conventional synthetic disease-modifying antirheumatic drugs: Analysis of data from the DRIVE and DESIRABLE studies. Mod Rheumatol. 2021 Jan;31(1):34-41. doi: 10.1080/14397595.2019.1703484. Epub 2020 Jan 9. PMID: 31826682. [3] Gorman JD, Lum RF, Chen JJ, Suarez-Almazor ME, Thomson G, Criswell LA. Impact of shared epitope genotype and ethnicity on erosive disease: a meta-analysis of 3,240 rheumatoid arthritis patients. Arthritis Rheum. 2004 Feb;50(2):400-12. doi: 10.1002/art.20006. PMID: 14872482. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>