Association Between Chikungunya Infection and Rheumatoid Arthritis in Taiwan—A Cross‐Sectional Study

OBJECTIVES: Chikungunya virus (CHIKV) infection might cause chronic chikungunya arthritis resembling rheumatoid arthritis (RA). The purpose of this study is to investigate the potential role of this virus in the pathogenesis of RA in Taiwan, a non-endemic area. METHODS: This cross-sectional study enrolled 98 RA patients and 200 healthy controls. Serum CHIKV IgM and IgG were tested using two commercial enzyme-linked immunosorbent assay (ELISA) kits (Abcam and Euroimmun) and an in-house neutralization assay. ELISA-IgM was performed only in patients with RA. ELISA or neutralization positive samples were further tested for CHIKV RNA by reverse-transcription-polymerase chain reaction. Associations between CHIKV seropositivity and various autoantibodies were analyzed. The agreements among these assays were also evaluated. RESULTS: Neutralizing antibodies were detected in 2 of 98 RA patients and in none of the controls (p = 0.107, Fisher's exact test; p = 0.043, chi-square). Both patients were absent from Abcam-IgM and -IgG, as well as Euroimmun-IgM and -IgG testing. There was no association between Abcam-IgM or Euroimmun-IgM and rheumatoid factor, anti-cyclic citrullinated peptide, antinuclear, or anti-extractable nuclear antigen antibodies. Poor agreements were noted between the neutralizing assay and Abcam-IgG or Euroimmun-IgG (κ = 0 and 0, respectively). A similar finding was also found between Abcam-IgM and Euroimmun-IgM (κ = -0.38). CONCLUSION: Our study was not sufficiently powered to establish a causal association between CHIKV infection and RA development. Poor agreements were noted among different commercial ELISA kits and neutralization assays, underscoring the limitations of the serology assay.