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

Samantha Ansah-Dico, Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, District of Columbia, USA.
Ilana Heckler, Department of Scientific Affairs, EUROIMMUN US, Mountain Lakes, New Jersey, USA.
Michelle Premazzi Papa, Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, District of Columbia, USA.
Alfonso Sucerquia Hernández, Department of Medicine, George Washington University, Washington, D.C., USA.
Jose Forero Mejía, Department of Medicine, George Washington University, Washington, D.C., USA.
Sarah Renee Tritsch, Global Health, Milken Institute School of Public Health, George Washington University, Washington, D.C., USA.
Evelyn Mendoza-Torres, Advanced Biomedicine Research Group, Faculty of Health, Exact and Natural Sciences, Universidad Libre de Colombia, Barranquilla, Atlantico, Colombia.
Liliana Encinales, Department of Medicine, Allied Research Society, Barranquilla, Atlántico, Colombia.
Andres Cadena Bonfanti, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
Abigale Marie Proctor, Global Health, Milken Institute School of Public Health, George Washington University, Washington, D.C., USA.
Jessica M. Wells, Department of Quality Operations, EUROIMMUN US, Mountain Lakes, New Jersey, USA.
Daniela Díaz Hernández, Pediatrics Department, Faculty of Health, Exact and Natural Sciences, Universidad Libre de Colombia, Seccional Barranquilla, Barranquilla, Atlántico, Colombia.
Juan Manuel Pretelt Gazabon, Internal Medicine Department. Faculty of Health, Exact and Natural Sciences, Universidad Libre de Colombia, Seccional Barranquilla, Barranquilla, Atlántico, Colombia.
Mónica Gómez Pulido, Microbiology Department. Faculty of Health, Exact and Natural Sciences, Universidad Libre de Colombia, Seccional Barranquilla, Barranquilla, Atlántico, Colombia.
Sara Camila Castiblanco-Arroyave, Internal Medicine Department. Faculty of Health, Exact and Natural Sciences, Universidad Libre de Colombia, Seccional Barranquilla, Barranquilla, Atlántico, Colombia.
Sammuel Joseph Simmens, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University Milken Institute School of Public Health, Washington, D.C., USA.
Rebecca Lynch, Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, District of Columbia, USA.
Aileen Yu-Hen Chang, Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, District of Columbia, USA.

Document Type

Journal Article

Publication Date

4-1-2025

Journal

Microbiology spectrum

Volume

13

Issue

4

DOI

10.1128/spectrum.02656-24

Keywords

antibodies; arthritis; arthritis disease severity; autoantibodies; chikungunya virus

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.

Department

Microbiology, Immunology, and Tropical Medicine

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