Background

Programmed cell death (PD)-1 and its ligand (PD-L1) plays crucial roles in T-cell tolerance as immune checkpoint. Previous studies reported that increased serum levels of soluble PD-L1 (sPD-L1) reflect myocardial and vascular inflammation. However, little is known about the clinical relationship between sPD-L1 and acute coronary syndrome (ACS). We investigated the relation of sPD-L1 and ACS.

Methods

We prospectively measured serum levels of sPD-L1 using a commercially available enzyme-linked immunosorbent assay kit in patients with coronary artery disease (CAD) and continuous non-CAD admitted to Kumamoto University Hospital between December 2017 and June 2019. All malignant diseases, patients who underwent hemodialysis, active collagen diseases, and severe infectious diseases were excluded.

Results

Totally, 446 CAD patients [ACS, n = 124; chronic coronary syndrome (CCS), n = 322] and 24 non-CAD patients were analyzed. The levels of sPD-L1 were significantly higher in patients with ACS than those both with non-CAD and CCS {ACS, 188.7 (111.0–260.8) pg/mL, p < 0.001 vs. non-CAD [83.5 (70.8–130.4) pg/mL]; and p = 0.009 vs. CCS [144.2 (94.8–215.5) pg/mL], respectively}. Univariate logistic regression analysis identified that sPD-L1 was significantly associated with ACS [odds ratio (OR): 1.459, 95% confidence interval (CI): 1.198–1.778, p < 0.001]. Multivariable logistic regression analysis with nine significant factors identified from the univariate analysis revealed that sPD-L1 was significantly and independently associated with ACS (OR: 1.561, 95% CI: 1.215–2.006, p < 0.001).

Conclusions

This is the first clinical study to demonstrate the increased level of sPD-L1 in patients with CAD, and the significant association with ACS.

中文翻译：

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增加的可溶性程序性细胞死亡配体 1 与急性冠状动脉综合征有关

背景

程序性细胞死亡 (PD)-1 及其配体 (PD-L1) 作为免疫检查点在 T 细胞耐受中起着至关重要的作用。以前的研究报道，可溶性 PD-L1 (sPD-L1) 的血清水平升高反映了心肌和血管炎症。然而，关于 sPD-L1 与急性冠状动脉综合征 (ACS) 之间的临床关系知之甚少。我们研究了 sPD-L1 和 ACS 的关系。

方法

我们使用市售的酶联免疫吸附测定试剂盒前瞻性地测量了 2017 年 12 月至 2019 年 6 月熊本大学医院收治的冠状动脉疾病 (CAD) 和连续非 CAD 患者的血清 sPD-L1 水平。所有恶性疾病，患者排除接受过血液透析、活动性胶原病、严重感染性疾病的患者。

结果

总共有 446 名 CAD 患者 [ACS，n  = 124；分析了慢性冠状动脉综合征 (CCS)，n  = 322] 和 24 名非 CAD 患者。ACS 患者的 sPD-L1 水平显着高于非 CAD 和 CCS 患者{ACS, 188.7 (111.0–260.8) pg/mL, p  < 0.001 vs. non-CAD [83.5 (70.8–130.4)皮克/毫升]; 和p  = 0.009 vs. CCS [144.2 (94.8–215.5) pg/mL]，分别}。单变量逻辑回归分析确定 sPD-L1 与 ACS 显着相关 [优势比 (OR): 1.459, 95% 置信区间 (CI): 1.198–1.778, p < 0.001]。从单变量分析中确定的九个重要因素的多变量逻辑回归分析显示，sPD-L1 与 ACS 显着且独立相关（OR：1.561，95% CI：1.215-2.006，p  < 0.001）。

结论

这是第一项证明 CAD 患者 sPD-L1 水平升高以及与 ACS 显着相关的临床研究。