T细胞活化免疫球蛋白抑制V型结构域在幼年特发性关节炎中作用的初步研究

A preliminary study on the role of V-domain Ig suppressor of T cell activation in juvenile idiopathic arthritis

摘要:

目的 分析T细胞活化免疫球蛋白抑制V型结构域（V-domain Ig suppressor of T cell activation，VISTA）在幼年特发性关节炎（juvenile idiopathic arthritis，JIA）患儿外周血的表达情况，探讨其在发病中的作用。方法 前瞻性收集不同亚型JIA患儿（47例）及健康儿童（10例）的外周血，利用流式细胞术检测CD14⁺单核细胞、CD4⁺T淋巴细胞、CD8⁺T淋巴细胞上VISTA、干扰素-γ（interfern-γ，IFN-γ）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）的表达情况。结果 VISTA在JIA患儿中的表达水平比健康儿童低（P<0.05）；不同亚型JIA患儿VISTA表达差异有统计学意义，以全身型表达水平最低（P<0.05）；不同免疫细胞表达VISTA差异有统计学意义，单核细胞表面VISTA表达水平更高（P<0.05）。相关性分析发现CD4⁺T细胞上VISTA与IFN-γ（r=-0.436，P<0.05）、TNF-α（r=-0.382，P<0.05）表达呈负相关，CD8⁺T细胞上VISTA与IFN-γ（r=-0.348，P<0.05）、TNF-α（r=-0.487，P<0.05）表达呈负相关；CD14⁺单核细胞上VISTA与IFN-γ（r=-0.582，P<0.05）、TNF-α（r=-0.603，P<0.05）表达呈负相关。结论 VISTA表达不足可能与JIA发病相关，增强VISTA的免疫调节作用可能是未来治疗JIA的途径之一。

Abstract:

Objective To study the expression of V-domain Ig suppressor of T cell activation (VISTA) in peripheral blood of children with juvenile idiopathic arthritis (JIA) and its role in the pathogenesis of JIA.Methods In this prospective study, peripheral blood was collected from 47 children with different subtypes of JIA and 10 healthy children. Flow cytometry was used to measure the expression levels of VISTA, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) on CD14⁺ mononuclear cells, CD4⁺ T lymphocytes, and CD8⁺ T lymphocytes.Results The children with JIA had a significantly lower expression level of VISTA than the healthy children (P<0.05). There was a significant difference in the expression of VISTA between the children with different subtypes of JIA, with the lowest expression level in those with systemic JIA (P<0.05). There was also a significant difference in the expression of VISTA between different immune cells, with a significantly higher expression level on the surface of monocytes (P<0.05). Correlation analysis showed that VISTA was negatively correlated with the expression of IFN-γ and TNF-α on CD4⁺ T cells (r=-0.436 and -0.382 respectively, P<0.05), CD8⁺ T cells (r=-0.348 and -0.487 respectively, P<0.05), and CD14⁺ mononuclear cells (r=-0.582 and -0.603 respectively, P<0.05).Conclusions The insufficient expression of VISTA may be associated with the pathogenesis of JIA, and enhancing the immunomodulatory effect of VISTA might be one option for the treatment of JIA in the future.