AUTHOR=Dobbs John E. , Tritsch Sarah R. , Encinales Liliana , Cadena Andres , Suchowiecki Karol , Simon Gary , Mores Christopher , Insignares Silvana , Orozco Vierys Patricia Villamil , Ospino Mirna , Echavez Lil Avendano , Gomez Carlos Andres Herrera , Crespo Yerlenis Galvis , Amdur Richard , Jimenez Alberto David Cabana , Hernandez Carlos Alberto Perez , Zapata Jennifer Carolina Martinez , Hernandez Alfonso Sucerquia , Silvera Paula Bruges , Rosales Wendy , Mendoza Evelyn , Osorio-Llanes Estefanie , Castellar Jairo , Jimenez Dennys , Cooper Dan M. , Firestein Gary S. , Martins Karen , Chang Aileen Y. TITLE=Regulatory T-cells and GARP expression are decreased in exercise-associated chikungunya viral arthritis flares JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1007106 DOI=10.3389/fimmu.2022.1007106 ISSN=1664-3224 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.