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. 2022 Oct 7:13:1007106.
doi: 10.3389/fimmu.2022.1007106. eCollection 2022.

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

John E Dobbs  1 , Sarah R Tritsch  2 , Liliana Encinales  3 , Andres Cadena  4 , Karol Suchowiecki  1 , Gary Simon  1 , Christopher Mores  2 , Silvana Insignares  3 , Vierys Patricia Villamil Orozco  3 , Mirna Ospino  3 , Lil Avendano Echavez  4 , Carlos Andres Herrera Gomez  4 , Yerlenis Galvis Crespo  4 , Richard Amdur  1 , Alberto David Cabana Jimenez  4 , Carlos Alberto Perez Hernandez  4 , Jennifer Carolina Martinez Zapata  4 , Alfonso Sucerquia Hernandez  4 , Paula Bruges Silvera  4 , Wendy Rosales  4 , Evelyn Mendoza  3   5 , Estefanie Osorio-Llanes  5 , Jairo Castellar  5 , Dennys Jimenez  6 , Dan M Cooper  7 , Gary S Firestein  8 , Karen Martins  9 , Aileen Y Chang  1
Affiliations

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

John E Dobbs et al. Front Immunol. .

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 via 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.

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

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Conflict of interest statement

Authors LE, SI, VO, MO, and EM, were/are employed by the Allied Research Society. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Treg Gating Strategy.
See this image and copyright information in PMC

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