The role of IL-2 therapy for Relapsing-Remitting Chikungunya Arthritis

摘要 基孔肯雅病毒(CHIKV)是一种由蚊子传播的甲型病毒，可导致持续性关节炎 大约四分之一的患者。目前还没有针对CHIKV的循证标准治疗 慢性关节炎。在目前的提案中，我们试图确定复发的治疗靶点--缓解性关节炎 与CHIKV感染有关。我们的哥伦比亚队列(n=500)受CHIKV影响的患者提供了 这是进一步了解CHIKV关节炎爆发免疫学的难得机会。我们的初步数据 提示调节性T细胞(Treg)功能改变可能在CHIKV关节炎发病机制中起一定作用。 以小剂量白介素2(IL-2)为基础的治疗自身免疫性疾病的新疗法被证明上调 Tregs和可能在CHIKV关节炎发作中使用。我们的主要目标是进一步了解IL-2在 CHIKV关节炎中的Treg种群。我们的中心假设是慢性CHIKV关节炎活动 与IL-2介导的Treg水平低下和小剂量IL-2相关，是一种潜在的治疗方法。这 假设将在两个特定的目标下进行评估。在目标1中，我们将描述IL-2在Treg扩展中的作用 与非关节炎相比，CHIKV关节炎发作与缓解期间相应的关节炎严重程度 控制。在目标2中，我们将确定IL-2疗法在小鼠CHIKV关节炎治疗中的作用 模特。这项研究的影响将确定Tregs和CHIKV相关的相关性 关节痛。它可能为小剂量IL-2治疗CHIKV关节炎提供临床前评估和对 这种新疗法的使用一般用于治疗病毒性关节炎。

ABSTRACT Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that causes persistent arthritis in approximately one-fourth of patients. There is currently no evidence-based standard treatment for CHIKV chronic arthritis. In the current proposal, we seek to identify a therapeutic target for relapsing-remitting arthritis associated with CHIKV infection. Our Colombian cohort (n = 500) of patients affected by CHIKV affords a unique opportunity to further understand the immunology of CHIKV arthritis flares. Our preliminary data suggest that alteration of regulatory T cell (Treg) function may play a role in CHIKV arthritis pathogenesis. Novel low-dose interleukin-2 (IL-2) based therapies for autoimmune disease have been shown to up-regulate Tregs and may be of use in CHIKV arthritis flares. Our main goal is to further understand the role of IL-2 in Treg populations in CHIKV arthritis. Our central hypothesis is that chronic CHIKV arthritis activity is associated with deficient IL-2 mediated Treg levels and low-dose IL-2 is a potential therapeutic. This hypothesis will be evaluated in two specific aims. In Aim 1, we will describe the role of IL-2 in Treg expansion and corresponding arthritis severity during CHIKV arthritis flare vs. remission compared to non-arthritic controls. In Aim 2, we will determine the role of IL-2 therapy in the treatment of CHIKV arthritis in a mouse model. The impact of this research will determine the correlation between Tregs and CHIKV-associated arthralgia. It may provide a pre-clinical evaluation of low-dose IL-2 therapy for CHIKV arthritis and insights into the use of this novel therapeutic for viral arthritis in general.