The role of autoantibodies in post-chikungunya viral arthritis disease severity

Abstract

Post-chikungunya viral arthritis may persist for months to years after infection and is characterized by relapsing and remitting symptoms. This study investigates the relationship between autoantibodies and chikungunya arthritis severity, providing insights into arthritis pathogenesis. We assessed arthritis measures in a cohort of serologically confirmed chikungunya cases from Colombia between 2019 and 2021 (n = 144). We measured arthritis disease severity, flare intensity, pain, and disability, then plasma antibody levels of rheumatoid factor IgM, anti-cyclic citrullinated peptide (CCP), anti-citrullinated α-enolase peptide 1 (CEP-1), anti-nuclear antibody (ANA), anti-citrullinated vimentin (Sa), and immunoglobulins produced in response to chikungunya, Zika and Mayaro. Finally, we examined the correlation between the arthritis measures with the titers of antibodies hypothesized to play a potential role in arthritis pathogenesis. Cases were characterized by moderate disease severity (Disease Activity Score-28 mean, 3.66 ± 1.23) in current arthritis flare with moderate intensity (Flare Score, 25.42 ± 12.38), moderate pain (61.47 ± 27.23 on visual analog scale 0-100), and some disability (Health Assessment Questionnaire 0.77 ± 0.58). After Bonferroni adjustment, there were no statistically significant correlations between the levels of antibodies and arthritis measures. Weak correlations between rheumatoid factor IgM with arthritis severity and pain (P < 0.01) and anti-CEP1 with disability (P < 0.05) were observed when unadjusted for multiple comparisons. The data suggest that autoantibodies, such as RF, anti-CCP, and anti-CEP-1, do not correlate with post-chikungunya arthritis disease severity, thus unlikely to significantly contribute to pathogenesis. Exposure to other arboviral infections was not related to worse post-chikungunya arthritis. This suggests that other pathways for arthritis disease pathogenesis should be examined.IMPORTANCEThis cohort study describes the correlation between levels of autoantibodies, viral antibodies, and arthritis outcomes, suggesting that autoantibodies known to play an important role in other autoimmune diseases do not correlate with chikungunya arthritis relapse disease severity and are unlikely to contribute significantly to arthritis pathogenesis. This suggests that other pathways for arthritis disease pathogenesis should be examined to identify diagnostic and prognostic markers of alphaviral arthritis.

Keywords: antibodies; arthritis; arthritis disease severity; autoantibodies; chikungunya virus.

Fig 1

Comparison of demographic and arthritis measures by chikungunya IgM antibody status. Age, days of fever during initial chikungunya infection, pain intensity measured by the visual analog scale from 0 to 100, disease severity as measured by the Disease Activity Score-28, flare intensity measured by the Flare Score adapted for chikungunya (0–50) and disability measured by the Health Assessment Questionnaire were compared between cases positive versus negative for chikungunya IgM. No differences were significant as compared by the Mann–Whitney test (age: P = 0.52, days of fever: P = 0.35, pain intensity: P = 0.10, arthritis disease activity: P = 0.89, arthritis flare intensity: P = 0.26 and disability: P = 0.90).

Fig 2

Chikungunya and Mayaro IgG correlation.