Zhou Man, Dai Wen, Cui Yan, Liu Huan, Li Yan
Department of Clinical Laboratory, Wuhan University, Renmin Hospital, Wuhan 430060, China.
Ann Transl Med. 2020 Mar;8(6):379. doi: 10.21037/atm.2020.02.27.
As a major inflammatory pathway in coronary artery disease (CAD), IL-6 trans-signaling is activated by the IL-6: sIL-6Rα binary complex (B) and inhibited by sgp130 through forming the IL-6: sIL-6Rα: sgp130 ternary complex (T). The aim of the present study was to examine the possible relationship between biomarkers mirroring the IL-6-neutralizing sIL-6R-sgp130 buffer system and CAD in postmenopausal women.
Our study recruited 155 CAD patients and 181 controls among postmenopausal women. Circulating levels of IL-6, sIL-6Rα and sgp130 were detected using an enzyme-linked immunosorbent assay, and the B/T ratio was calculated by the specific formulas.
CAD patients showed significantly higher circulating levels of IL-6 and sIL-6Rα, significantly higher B/T ratio, and significantly lower sgp130 levels than controls (all P<0.05). Spearman's correlation analysis indicated that IL-6 levels (r=0.185, P<0.01) and B/T ratio (r=0.319, P<0.01) were positively related to Gensini scores, while elevated sgp130 levels were significantly associated with decreased Gensini scores (r=-0.565, P<0.001). In addition, multiple regression analysis showed that Gensini scores were negatively associated with serum sgp130 levels (β-coefficient =-0.318, P<0.001) and had a positive association with IL-6 levels (β-coefficient =0.138, P<0.05). Multivariate logistic regression analysis identified that after adjusting for confounding factors, higher sgp130 remained an independent predictor of lower incidence of CAD in women after menopause (OR =0.904; 95% CI: 0.837-0.976, P=0.010). Moreover, sgp130 levels at 136.01 ng/mL (AUC =0.957, 95% CI: 0.928-0.986, P<0.001) and B/T ratio at 1.51 (AUC =0.765; 95% CI: 0.702-0.828, P<0.001) were effective cut-off points to determine the presence of CAD based on receiver operating characteristic curves.
Based on this small case-control study, sgp130 and B/T ratio in the IL-6-neutralizing sIL-6R-sgp130 buffer system may be promising biomarkers for CAD diagnosis and assessments of coronary stenosis severity in postmenopausal women.
作为冠状动脉疾病（CAD）中的一条主要炎症途径，白细胞介素-6（IL-6）转信号传导由IL-6：可溶性IL-6受体α（sIL-6Rα）二元复合物（B）激活，并通过形成IL-6：sIL-6Rα：可溶性糖蛋白130（sgp130）三元复合物（T）被sgp130抑制。本研究的目的是探讨反映IL-6中和性sIL-6R-sgp130缓冲系统的生物标志物与绝经后女性CAD之间的可能关系。
我们的研究招募了155名绝经后女性CAD患者和181名对照者。采用酶联免疫吸附测定法检测循环中IL-6、sIL-6Rα和sgp130的水平，并通过特定公式计算B/T比值。
与对照组相比，CAD患者的循环中IL-6和sIL-6Rα水平显著更高，B/T比值显著更高，而sgp130水平显著更低（均P<0.05）。Spearman相关性分析表明，IL-6水平（r=0.185，P<0.01）和B/T比值（r=0.319，P<0.01）与Gensini评分呈正相关，而sgp130水平升高与Gensini评分降低显著相关（r=-0.565，P<0.001）。此外，多元回归分析显示，Gensini评分与血清sgp130水平呈负相关（β系数=-0.318，P<0.001），与IL-6水平呈正相关（β系数=0.138，P<0.05）。多因素logistic回归分析确定，在调整混杂因素后，较高的sgp130仍然是绝经后女性CAD发病率较低的独立预测因素（OR =0.904；95%CI：0.837-0.976，P=0.010）。此外，基于受试者工作特征曲线，sgp130水平为136.01 ng/mL（AUC =0.957，95%CI：0.928-0.986，P<0.001）和B/T比值为1.51（AUC =0.765；95%CI：0.702-0.828，P<0.001）是确定CAD存在的有效切点。
基于这项小型病例对照研究，IL-6中和性sIL-6R-sgp130缓冲系统中的sgp130和B/T比值可能是绝经后女性CAD诊断和冠状动脉狭窄严重程度评估的有前景的生物标志物。
