Title

Regulatory T-cells and GARP expression are decreased in exercise-associated chikungunya viral arthritis flares

Authors

John E. Dobbs, School of Medicine and Health Sciences, The George Washington University, Washington, DC, United States.
Sarah R. Tritsch, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States.
Liliana Encinales, Allied Research Society, Barranquilla, Colombia.
Andres Cadena, Clinica de la Costa, Barranquilla, Colombia.
Karol Suchowiecki, School of Medicine and Health Sciences, The George Washington University, Washington, DC, United States.
Gary Simon, School of Medicine and Health Sciences, The George Washington University, Washington, DC, United States.
Christopher Mores, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States.
Silvana Insignares, Allied Research Society, Barranquilla, Colombia.
Vierys Patricia Orozco, Allied Research Society, Barranquilla, Colombia.
Mirna Ospino, Allied Research Society, Barranquilla, Colombia.
Lil Avendano Echavez, Clinica de la Costa, Barranquilla, Colombia.
Carlos Andres Gomez, Clinica de la Costa, Barranquilla, Colombia.
Yerlenis Galvis Crespo, Clinica de la Costa, Barranquilla, Colombia.
Richard Amdur, School of Medicine and Health Sciences, The George Washington University, Washington, DC, United States.
Alberto David Jimenez, Clinica de la Costa, Barranquilla, Colombia.
Carlos Alberto Hernandez, Clinica de la Costa, Barranquilla, Colombia.
Jennifer Carolina Zapata, Clinica de la Costa, Barranquilla, Colombia.
Alfonso Sucerquia Hernandez, Clinica de la Costa, Barranquilla, Colombia.
Paula Bruges Silvera, Clinica de la Costa, Barranquilla, Colombia.
Wendy Rosales, Clinica de la Costa, Barranquilla, Colombia.
Evelyn Mendoza, Allied Research Society, Barranquilla, Colombia.
Estefanie Osorio-Llanes, Universidad Libre, Barranquilla, Colombia.
Jairo Castellar, Universidad Libre, Barranquilla, Colombia.
Dennys Jimenez, University of Texas Health Science Center San Antonio, TX, United States.
Dan M. Cooper, University of California Irvine, Irvine, CA, United States.
Gary S. Firestein, University of California- San Diego, San Diego, CA, United States.
Karen Martins, Biomedical Advanced Research and Development Authority, Bethesda, MD, United States.
Aileen Y. Chang, School of Medicine and Health Sciences, The George Washington University, Washington, DC, United States.

Document Type

Journal Article

Publication Date

1-1-2022

Journal

Frontiers in immunology

Volume

13

DOI

10.3389/fimmu.2022.1007106

Keywords

GARP; chikungunya; chikungunya arthritis; clinical trials; exercise; immunology & infectious diseases; inflammation; viral arthritis

Abstract

Objective: Chikungunya virus (CHIKV) causes persistent arthritis, and our prior study showed that approximately one third of CHIKV arthritis patients had exacerbated arthritis associated with exercise. The underlying mechanism of exercise-associated chikungunya arthritis flare (EACAF) is unknown, and this analysis aimed to examine the regulatory T-cell immune response related to CHIKV arthritis flares. Methods: In our study, 124 Colombian patients with a history of CHIKV infection four years prior were enrolled and 113 cases with serologically confirmed CHIKV IgG were used in this analysis. Patient information was gathered questionnaires, and blood samples were taken to identify total live peripheral blood mononuclear cells, CD4+ cells, T regulatory cells, and their immune markers. We compared outcomes in CHIKV patients with (n = 38) vs. without (n = 75) EACAF using t-tests to assess means and the Fisher's exact test, chi-squared to evaluate categorical variables, and Kruskal-Wallis tests in the setting of skewed distributions (SAS 9.3). Results: 33.6% of CHIKV cases reported worsening arthritis with exercise. EACAF patients reported higher global assessments of arthritis disease ranging from 0-100 (71.2 ± 19.7 vs. 59.9 ± 28.0, p=0.03). EACAF patients had lower ratios of T regulatory (Treg)/CD4+ T-cells (1.95 ± 0.73 vs. 2.4 ± 1.29, p = 0.04) and lower percentage of GARP (glycoprotein-A repetitions predominant) expression per Treg (0.13 ± 0.0.33 vs. 0.16 ± 0.24 p= 0.020). Conclusion: These findings suggest relative decreases in GARP expression may indicate a decreased level of immune suppression. Treg populations in patients with CHIKV arthritis may contribute to arthritis flares during exercise, though current research is conflicting.

Department

Medicine

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