Department of Rheumatology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
Rheumatology (Oxford). 2019 Mar 1;58(3):502-510. doi: 10.1093/rheumatology/key348.
This study aimed to assess the potential role of the TNF superfamily member lymphocyte T-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) in SSc through evaluation of: skin expression of LIGHT and its receptors, herpesvirus entry mediator and lymphotoxin ß-related receptor, and serum concentration of LIGHT in SSc patients.
Expression of LIGHT and its receptors was investigated by immunohistochemistry and evaluated semi-quantitatively in skin biopsies from 19 SSc patients and 9 healthy controls. Serum levels of LIGHT were measured using ELISA in 329 patients with SSc and 50 control subjects.
Expression of LIGHT and both receptors was higher in SSc patients compared with controls (P < 0.05 for all comparisons). Patients with early SSc (⩽ 3 years from the first non-Raynaud's phenomenon symptom) showed higher expression of LIGHT and herpesvirus entry mediator compared with patients with longer disease duration (P < 0.05 for both comparisons). The mean serum concentration of LIGHT was significantly higher in SSc patients compared with the controls (P < 0.05). High serum concentration of LIGHT was associated with male sex, presence of digital ulcers, muscle involvement (defined by elevated serum creatine kinase levels), steroid treatment and lack of ACA. However, in multivariate regression analysis only presence of digital ulcers and creatine kinase elevation were independently associated with serum concentration of LIGHT.
These data provide the first evidence of overexpression of LIGHT and its receptors in SSc and suggest that the LIGHT axis might contribute to the pathogenesis of SSc. Increased serum concentrations of LIGHT seem to reflect vascular injury in SSc.
通过评估 TNF 超家族成员淋巴细胞 T 相关诱导配体（与疱疹病毒进入介体竞争结合糖蛋白 D 的配体）在 T 细胞上的表达（LIGHT），研究其在系统性硬化症（SSc）中的潜在作用。方法：采用免疫组化法检测 19 例 SSc 患者和 9 例健康对照者皮肤活检组织中 LIGHT 及其受体、疱疹病毒进入介体和淋巴毒素β相关受体的表达，并采用 ELISA 法检测 329 例 SSc 患者和 50 例对照者血清 LIGHT 浓度。结果：与对照组相比，SSc 患者的 LIGHT 及其受体表达均升高（所有比较 P＜0.05）。早期 SSc（从首发非雷诺现象症状起≤3 年）患者的 LIGHT 和疱疹病毒进入介体表达高于疾病持续时间较长的患者（两种比较 P＜0.05）。与对照组相比，SSc 患者血清 LIGHT 平均浓度显著升高（P＜0.05）。血清 LIGHT 浓度较高与男性、存在指溃疡、肌肉受累（定义为血清肌酸激酶水平升高）、皮质类固醇治疗和 ACA 阴性有关。然而，多元回归分析显示，仅指溃疡和肌酸激酶升高与血清 LIGHT 浓度独立相关。结论：这些数据首次提供了 LIGHT 及其受体在 SSc 中过度表达的证据，并提示 LIGHT 轴可能有助于 SSc 的发病机制。血清 LIGHT 浓度的增加似乎反映了 SSc 中的血管损伤。
