Cytokine and T cell responses in post-chikungunya viral arthritis: A cross-sectional study

Aileen Y. Chang, Department of Medicine, George Washington University, Washington, DC, United States of America.
Sarah R. Tritsch, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC, United States of America.
Carlos Andres Herrera Gomez, Department of Medicine, George Washington University, Washington, DC, United States of America.
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.
Wendy Rosales, Advanced Biomedicine Research Group, Universidad Libre de Colombia, Seccional Barranquilla, Barranquilla, Atlántico, Colombia.
Evelyn Mendoza-Torres, Advanced Biomedicine Research Group, Universidad Libre de Colombia, Seccional Barranquilla, Barranquilla, Atlántico, Colombia.
Samuel Simmens, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington, DC, United States of America.
Richard L. Amdur, Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, United States of America.
Christopher N. Mores, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC, United States of America.
Paige Fierbaugh, Department of Medicine, George Washington University, Washington, DC, United States of America.
Carlos Alberto Perez Hernandez, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
Geraldine Avendaño, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
Paula Bruges Silvera, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
Yerlenis Galvis Crespo, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
Alberto David Jimenez, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
Jennifer Carolina Martinez Zapata, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
Dennys Jimenez, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
Estefanie Osorio-Llanes, Advanced Biomedicine Research Group, Universidad Libre de Colombia, Seccional Barranquilla, Barranquilla, Atlántico, Colombia.
Jairo Castellar-Lopez, Advanced Biomedicine Research Group, Universidad Libre de Colombia, Seccional Barranquilla, Barranquilla, Atlántico, Colombia.
Karol Suchowiecki, Department of Medicine, George Washington University, Washington, DC, United States of America.
Karen Martins, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America.
Melissa Gregory, Henry M. Jackson Foundation, In Support of Austere Environments Consortium for Enhanced Sepsis Outcomes (ACESO), Bethesda, Maryland, United States of America.
Ivan Zuluaga, Universidad Libre de Barranquilla, Clínica Iberoamérica, Barranquilla, Atlántico, Colombia.
Abigale Proctor, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC, United States of America.
Alfonso Sucerquia Hernández, Department of Medicine, George Washington University, Washington, DC, United States of America.
Leandro Sierra-Carrero, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
Maria Villanueva Colpas, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
Juan Carlos Hernandez, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
Andres Alberto Quast, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
Joaquin Andres De Barros, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.
José Forero Mejía, Centro de Investigación, Clínica de la Costa SAS, Barranquilla, Atlántico, Colombia.

Document Type

Journal Article

Publication Date

1-1-2024

Journal

PloS one

Volume

19

Issue

3

DOI

10.1371/journal.pone.0299521

Abstract

OBJECTIVE: To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. METHODS: Participants with chikungunya arthritis were recruited from Colombia from 2019-2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. RESULTS: Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). CONCLUSION: Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.

Department

Medicine

Link to Full Text

Share

COinS