From the *Department of Cardiology, Gazi University Faculty of Medicine; †Cardiology Department, Ankara Turkiye Yuksek Ihtisas Hospital; and ‡Department of Immunology, Immunology Research Center, Gazi University Faculty of Medicine, Ankara, Turkey.
J Investig Med. 2014 Jan;62(1):78-83. doi: 10.2310/JIM.0000000000000023.
Autoimmunity plays an essential role in the pathogenesis of rheumatic heart disease (RHD); however, cellular mechanisms of autoimmune response are unclear. Whereas T helper 17 (TH17) and regulatory T cells (Treg) cells share a common differentiation pathway, they play opposite roles in the immune tolerance and autoimmune diseases. Although high TH17/Treg ratio has been shown in several autoimmune diseases, no data are available in RHD. This study investigated the balance between TH17 and Treg in rheumatic mitral valve disease (MVD).
Forty patients with rheumatic MVD and 23 control subjects were enrolled into the study. All subjects underwent clinical, electrocardiographic, and echocardiographic evaluation. The percentages of circulating TH17 and Treg cells were analyzed by flow cytometry. Serum levels of high-sensitivity C-reactive protein (hs-CRP) and cytokines were assessed by enzyme-linked immunosorbent assay.
As compared with control subjects, rheumatic MVD patients showed significant increase in peripheral TH17 percentage, high serum levels of TH17-related cytokine interleukin 17A, and an obvious decrease in the percentage of Treg cells. T helper 17/Treg ratio was significantly high in rheumatic MVD patients compared with control subjects (P = 0.0001). Serum concentrations of hs-CRP in rheumatic MVD group were higher than those of the control subjects, and hs-CRP levels correlated with the TH17/Treg ratio (r = 0.71, P = 0.0001). Serum levels of transforming growth factor β1 were increased in rheumatic MVD group compared with those of the control subjects.
The results indicated that high TH17/Treg ratio exists inrheumatic MVD. This imbalance may play a role in the pathogenesis, and TH17/Treg balance may be a promising therapeutic approach in RHD.
自身免疫在风湿性心脏病（RHD）的发病机制中起着至关重要的作用；然而，自身免疫反应的细胞机制尚不清楚。辅助性 T 细胞 17（TH17）和调节性 T 细胞（Treg）细胞具有共同的分化途径，但它们在免疫耐受和自身免疫性疾病中发挥相反的作用。尽管在几种自身免疫性疾病中已经显示出高 TH17/Treg 比值，但在 RHD 中尚无数据。本研究探讨了风湿性二尖瓣疾病（MVD）中 TH17 和 Treg 之间的平衡。
纳入 40 例风湿性 MVD 患者和 23 例对照者。所有受试者均接受临床、心电图和超声心动图评估。通过流式细胞术分析循环 TH17 和 Treg 细胞的百分比。通过酶联免疫吸附试验测定血清高敏 C 反应蛋白（hs-CRP）和细胞因子水平。
与对照组相比，风湿性 MVD 患者外周血 TH17 百分比明显升高，TH17 相关细胞因子白细胞介素 17A 的血清水平明显升高，Treg 细胞的百分比明显降低。风湿性 MVD 患者的 TH17/Treg 比值明显高于对照组（P=0.0001）。风湿性 MVD 组血清 hs-CRP 浓度高于对照组，hs-CRP 水平与 TH17/Treg 比值相关（r=0.71，P=0.0001）。风湿性 MVD 组转化生长因子β1 的血清水平高于对照组。
结果表明风湿性 MVD 存在高 TH17/Treg 比值。这种失衡可能在发病机制中起作用，TH17/Treg 平衡可能是 RHD 的一种有前途的治疗方法。
