Atta-ur-Rahman School of Applied Biosciences, National University of Sciences & Technology, Islamabad, Pakistan.
Department of Biotechnology, Abdul Wali Khan University Mardan, Pakistan.
Cytokine. 2018 Apr;104:130-135. doi: 10.1016/j.cyto.2017.10.002. Epub 2017 Oct 7.
Genome-wide association studies have identified various susceptibility variants and loci associated with incidence of rheumatoid arthritis (RA) in different populations. One of these is T cell activation Rho GTPase activating protein (TAGAP). The present study sought to measure the expression of TAGAP in RA patients, CD4 T cells subsets from healthy humans and in mice with collagen-induced arthritis. Peripheral blood mononuclear cells (PBMC) from RA patients and tissues of arthritic mice at different stages of the disease were used for the evaluation of TAGAP mRNA expression. Increased TAGAP expression was observed in RA patients compared to healthy controls, and there were differences in the expression level of TAGAP in the tissues of mice with experimental arthritis. Gene expression in CD4 T cells from healthy humans was greatest 4 h after activation and protein expression was greatest after 24 h. The expression of TAGAP was not correlated with CD4 lymphocyte subsets which were enriched for functionally defined subsets (Th17, Treg, Th1), further indicating its utility as an indicator of lymphocyte activation. These findings indicate that increased TAGAP expression is a distinguishing feature of inflammatory disease and further highlight the role of TAGAP in RA susceptibility.
全基因组关联研究已经确定了各种与类风湿关节炎（RA）发病相关的易感变体和基因座，这些变体和基因座在不同人群中存在差异。其中之一是 T 细胞活化 Rho GTP 酶激活蛋白（TAGAP）。本研究旨在测量 RA 患者、健康人 CD4 T 细胞亚群和胶原诱导性关节炎小鼠中 TAGAP 的表达。使用 RA 患者的外周血单核细胞（PBMC）和疾病不同阶段的关节炎小鼠组织来评估 TAGAP mRNA 的表达。与健康对照相比，RA 患者的 TAGAP 表达增加，并且实验性关节炎小鼠组织中 TAGAP 的表达水平存在差异。健康人 CD4 T 细胞的基因表达在激活后 4 小时最高，蛋白表达在 24 小时最高。TAGAP 的表达与富含功能定义亚群（Th17、Treg、Th1）的 CD4 淋巴细胞亚群无关，这进一步表明其可用作淋巴细胞活化的指标。这些发现表明，TAGAP 表达增加是炎症性疾病的一个显著特征，并进一步强调了 TAGAP 在 RA 易感性中的作用。
