T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease
T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease
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DOI：
10.1002/art.23406
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发表时间：
2008-04-01
影响因子：
--
通讯作者：
Casolaro, Vincenzo
中科院分区：
文献类型：
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作者：
Boin, Francesco;De Fanis, Umberto;Casolaro, Vincenzo
Objective.肺部受累是系统性硬化症（SSc;硬皮病）发病率和死亡率的主要原因，间质性肺病（ILD）是最常见的肺部表现。假定异常的促纤维化Th 2/Tc 2极化T细胞应答介导组织损伤和纤维化。本研究的目的是调查是否极化T细胞表型在SSc与肺部疾病或其他临床表现的SSc。使用抗CD 3、CD 4、CD 8、趋化因子受体CCR 5（Th 1/Tc 1特异性）和抗Gr D-2受体CRTH 2（Jh 2/c2特异性）的抗体，通过流式细胞术对62例SSc患者和36例健康对照受试者的循环T细胞进行表征。使用CCR 5和CRTH 2 T细胞频率之间的比率来量化I型（高比率）或2型（低比率）免疫极化。SSc患者的CCR 5/CRTH 2 T细胞比率低于对照组（P < 0.0001），表明存在Th 2/Tc 2极化表型。与无ILD的SSc患者相比，在有ILD的SSc患者中观察到CCR 5/CRTH 2 T细胞比率显著降低（P < 0.0001），特别是与肺功能稳定的患者相比，在有活动性ILD的患者中（P <0.0001）。较低的CCR 5/CRTH 2比值与较低的预测用力肺活量百分比值密切相关（P < 0.0001）。在右心室收缩压>35 mm Hg的患者中，提示肺血管疾病，较低的预测弥散量百分比（DLCO）值与较高的CCR 5/CRTH 2 T细胞比率（Th 1/Tc 1）相关（P = 0.009），而在右心室收缩压> 35 mm Hg的患者中，
Objective. Lung involvement is the leading cause of morbidity and mortality in systemic sclerosis (SSc; scleroderma), and interstitial lung disease (ILD) is the most common pulmonary manifestation. An abnormal profibrotic Th2/Tc2-polarized T cell response is postulated to mediate tissue damage and fibrosis. The aim of this study was to investigate whether a polarized T cell phenotype in SSc is associated with lung disease or other clinical manifestations of SSc.Methods. Circulating T cells were characterized by flow cytometry in 62 patients with SSc and 36 healthy control subjects, using antibodies against CD3, CD4, CD8, chemokine receptor CCR5 (Th1/Tc1-specific), and grostaglandin D-2 receptor CRTH2 Jh2/c2-specific). The ratio between CCR5 and CRTH2 T cell frequencies was used to quantify type I (high-ratio) or type 2 (low-ratio) immune polarization.Results. Patients with SSc exhibited lower CCR5/CRTH2 T cell ratios than those exhibited by control subjects (P < 0.0001), indicating a Th2/Tc2-polarized phenotype. Markedly reduced CCR5/CRTH2 T cell ratios were observed in SSc patients with ILD compared with SSc patients without ILD (P < 0.0001), particularly in patients with active ILD (P < 0.0001) compared with those with stable lung function. Lower CCR5/CRTH2 ratios were strongly associated with a lower value for the percent predicted forced vital capacity (P < 0.0001). In patients with an estimated right ventricular systolic pressure >35 mm Hg, suggestive of pulmonary vascular disease, a lower value for the percent predicted diffusing capacity (DLCO) was associated with higher CCR5/CRTH2 T cell ratios (Th1/Tc1) (P = 0.009), while in those with right ventricular systolic pressure