Exposure to arboviral infections and risk of rheumatoid arthritis: Findings from the MyEIRA population-based case-control study

Abstract

Background: Rheumatoid arthritis (RA) is a chronic disease influenced by genetic and environmental factors, with viral infections potentially influencing the immune system and increasing the risk of autoimmune diseases like RA. This study investigated the relationship between exposure to chikungunya and dengue infections, indicated by the presence of arboviral IgG antibodies, and risk of developing RA dichotomized by anti-citrullinated protein antibody (ACPA) status. Methods: Serum samples from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study involving 1235 RA cases and 1625 controls were assayed for IgG antibodies against chikungunya and dengue viruses. Positive results indicate previous exposure to the studied arboviral infections. Logistic regression and Mann–Whitney U test were performed to estimate the risk of developing ACPA-positive/ACPA-negative RA. Results: We observed a low frequency of chikungunya IgG antibodies and a high frequency of dengue IgG antibodies in the overall RA cases and controls. No direct association was observed between previous exposure to chikungunya/dengue infection and risk of future RA in overall RA cases and controls. However, analysis by ethnicity showed a decreased risk for ACPA-positive RA in chikungunya IgG antibody positive subjects of Malay (odds ratio [OR] = 0.38, 95% confidence interval [CI] = 0.16–0.90, p < 0.05) and Chinese origins (OR = 0.12, 95% CI = 0.01–0.93, p < 0.05). Additionally, we observed a decreased risk of ACPA-positive RA in Indian among persons with positive dengue IgG antibody status (OR = 0.60, 95% CI = 0.38–0.95, p < 0.05). No significant association was observed between chikungunya/dengue infection exposures and risk of ACPA-negative RA. Conclusion: This study found no overall association between chikungunya or dengue exposure, and the risk for developing RA.