Journal Article

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

Hussein, Heselynn, Klareskog, Lars, Sulaiman, Wahinuddin, Said, Mohd‐Shahrir Mohamed, Ahmad, Siti Aisyah Abdul, Padyukov, Leonid, Mokhtar, Ainon Mohd, Too, Chun Lai, Mageswaran, Eashwary, Othman, Muhaini, Ali, Osman, Soo, Lau Ing, Alfredsson, Lars, Fauzi, Nurul‐Aain Ahmad, Rosman, Azmillah, Shahril, Nor‐Shuhaila, Chyn, Gun Suk, Tan, Lay Kim

2025

Overview

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. The Malaysian Epidemiological Investigation of Rheumatoid Arthritis population‐based case‐control study examined whether prior exposure to chikungunya and dengue viruses (via IgG seropositivity) is associated with rheumatoid arthritis (RA) risk, stratified by anti‐citrullinated protein antibody (ACPA) status. No overall association was found, but a reduced risk of ACPA‐positive RA was observed in specific ethnic groups. Key points With the availability of data from a large Asia population‐based case control study, namely the Malaysian Epidemiology Investigation of Rheumatoid Arthritis (MyEIRA), we investigated the relationships between anti‐arboviral antibodies (i.e., chikungunya and dengue) and different subsets of rheumatoid arthritis (RA), defined by anti‐citrullinated protein antibody (ACPA) status, and the risk of developing RA. In this study, low frequency of chikungunya IgG antibodies and high frequency of dengue IgG antibodies were found in both RA cases and controls. Ethnicity stratification analysis revealed decreased risk of developing ACPA‐positive RA in the Malays and Chinese with positive chikungunya IgG antibodies, and in Indians with positive dengue IgG antibodies, respectively. This study found no overall association between chikungunya or dengue exposure, and the risk for developing RA, whilst the inverse associations observed in RA with positive anti‐arboviral antibodies are in‐line with certain other studies investigating exposures to viral infections and RA risk.

• Publisher: Wiley
• Subject: chikungunya / dengue / exposure / rheumatoid arthritis / risk factor