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

Regulatory T-cells and GARP expression are decreased in exercise-associated chikungunya viral arthritis flares.
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DOI:
10.3389/fimmu.2022.1007106
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发表时间:
2022
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
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基孔肯雅病毒 (CHIKV) 会导致持续性关节炎,我们之前的研究表明,大约三分之一的 CHIKV 关节炎患者的关节炎与运动相关。运动相关基孔肯雅关节炎发作 (EACAF) 的潜在机制尚不清楚,本分析旨在检查与 CHIKV 关节炎发作相关的调节性 T 细胞免疫反应。在我们的研究中,纳入了四年前有 CHIKV 感染史的 124 名哥伦比亚患者,并在该分析中使用了 113 例经血清学证实的 CHIKV IgG 病例。通过问卷调查收集患者信息,并采集血液样本以鉴定总活外周血单核细胞、CD4+细胞、T调节细胞及其免疫标记物。我们使用 t 检验来评估均值,使用 Fisher 精确检验、卡方来评估分类变量,并在偏态分布 (SAS 9.3) 的情况下使用 Kruskal-Wallis 检验,比较了使用 (n = 38) 与未使用 (n = 75) EACAF 的 CHIKV 患者的结果。 33.6% 的 CHIKV 病例报告运动后关节炎恶化。 EACAF 患者报告的关节炎疾病总体评估较高,范围为 0-100(71.2 ± 19.7 对比 59.9 ± 28.0,p=0.03)。 EACAF 患者的调节性 T (Treg)/CD4+ T 细胞比率较低(1.95 ± 0.73 vs. 2.4 ± 1.29,p = 0.04),每个 Treg 的 GARP(糖蛋白 A 重复为主)表达百分比较低(0.13 ± 0.0.33 vs. 0.16 ± 0.24 p= 0.020)。这些发现表明 GARP 表达的相对减少可能表明免疫抑制水平降低。尽管目前的研究存在矛盾,但 CHIKV 关节炎患者的 Treg 群体可能会导致运动期间关节炎发作。
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. 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). 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). 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.
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