Soluble programmed cell death-ligand 1 as a new potential biomarker associated with acute coronary syndrome

Abstract

BackgroundSoluble programmed cell death-ligand 1 (sPD-L1) has been well documented to activate immunosuppression and is considered an essential predictor of negative clinical outcomes for several malignances and inflammatory conditions. However, the clinical significance of sPD-L1 in the peripheral blood of patients with coronary artery disease (CAD) remains unclear. The aim of this study was to assess the correlations of sPD-L1 with clinical features in CAD patients and evaluate the diagnostic value of this protein in CAD.MethodsA total of 111 CAD patients and 97 healthy volunteers who served as healthy controls (HCs) were consecutively enrolled. Plasma levels of sPD-L1 were measured with an amplified enzyme-linked immunosorbent assay (ELISA), and hs-CRP was measured with a C-reactive protein assay kit. The levels of other inflammatory cytokines were assessed in 88 CAD patients and 47 HCs by a multiparameter immunoluminescence flow cytometry detection technique. A logistic regression model was used to assess the independent association of sPD-L1 with acute coronary syndrome (ACS). The correlation between sPD-L1 and inflammatory cytokines in ACS was also assessed.ResultsPlasma levels of sPD-L1 were significantly increased in CAD patients, especially those with ACS. Univariate logistic regression analysis revealed that sPD-L1 (OR: 3.382, 95% CI: 2.249–5.084, p < 0.001), BMI, hypertension, diabetes, dyslipidemia, previous MI, and the levels of HDL-C, LDL-C and hs-CRP were significantly associated with ACS. sPD-L1 (OR: 3.336, 95% CI: 1.084–6.167, p = 0.001) was found to be independently and significantly associated with ACS in the subsequent multivariable logistic regression analysis. Additionally, elevated plasma sPD-L1 levels were associated with increased interleukin-6 and interleukin-8 levels in ACS patients. Receiver operating characteristic (ROC) analysis showed that the AUC of sPD-L1 for diagnosing ACS was 0.778, with a sensitivity of 73.9% and a specificity of 73.4%, which was comparable with that of the inflammatory biomarker hs-CRP.ConclusionThe plasma sPD-L1 level reflects the severity of CAD, is associated with inflammatory responses and is a potential new biomarker for the diagnosis of ACS.

Association of immunologic findings of atheromatous plaques with subsequent cardiovascular events in patients with peripheral artery disease

“…Recently, a higher rate of cardiovascular events after using immune checkpoint inhibitors was reported, which indirectly demonstrated the role of the PD-1/PD-L1 pathway in atherosclerosis 29 . Several studies have investigated the association between the blood level of soluble PD-L1 and acute coronary syndrome 13 , 30 . However, studies on the tissue expression of PD-L1 in atherosclerotic disease are limited.…”

Association between response to anti-PD-1 treatment and blood soluble PD-L1 and IL-8 changes in patients with NSCLC

“…The capture mAb-11E3 clearly performed as a blocking mAb that completely blocked PD-1 and PD-L1 binding, as also confirmed at the cellular level [ 40 ]. The detection mAb was nonblocking, and the sandwich ELISA established could detect and quantify functional sPD-L1 and had the same level of sensitivity and specificity as commercial kit [ 41 ]. Functional sPD-L1 not only induces lymphocyte exhaustion and benefits tumor evasion but also competes for membrane PD-1 binding sites available to anti-PD-1 mAbs.…”

Costimulatory and Coinhibitory Immune Checkpoints in Atherosclerosis

“… 107 soluble PD-L1 levels are increased in patients with CAD and reflect its severity. 108 , 109 The relevance of PD-1-PD-L1 interactions in human atherosclerosis became clear from the impact of PD-1/PD-L1/2 inhibition in patients treated for malignancies. Coinhibitory immune checkpoint inhibition was associated with an increased risk for cardiovascular events in oncology patients.…”