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可溶性内皮蛋白 C 受体(sEPCR)作为未经治疗的 HIV 感染患者在 ART 期间的炎症生物标志物。

Soluble endothelial protein C receptor (sEPCR) as an inflammatory biomarker in naive HIV-infected patients during ART.

机构信息

IRCCS San Raffaele Scientific Institute, Milan, Italy Università Vita-Salute San Raffaele, Medicina e Chirurgia, Milan, Italy

IRCCS San Raffaele Scientific Institute, Milan, Italy Università Vita-Salute San Raffaele, Medicina e Chirurgia, Milan, Italy.

出版信息

J Antimicrob Chemother. 2016 Jun;71(6):1627-31. doi: 10.1093/jac/dkw010. Epub 2016 Feb 16.

Abstract

BACKGROUND

After the advent of ART, non-AIDS-related comorbidities are the main causes of death in HIV patients. Multiple biomarkers have been studied as markers of disease. We wanted to test soluble endothelial protein C receptor (sEPCR) in an HIV setting.

OBJECTIVES

The primary objective was to determine whether sEPCR decreases after 48 weeks of ART in naive HIV patients. Secondary objectives were to compare sEPCR levels between patients with chronic HIV infection (CHI) and primary HIV infection (PHI) and to analyse if there is a correlation between sEPCR and both immunovirological parameters and different markers of inflammation.

PATIENTS AND METHODS

We analysed sEPCR in 33 patients with CHI and 19 patients with PHI naive to ART. sEPCR was compared together with immunovirological parameters (HIV RNA and CD4 cell count) and IL-6 or D-dimer (DD).

RESULTS AND CONCLUSIONS

After 48 weeks of ART, in CHI, the sEPCR decrease was significant (P = 0.0006) and sEPCR at baseline was correlated with both CD4 cell increase (r = +0.463, P = 0.007) and HIV RNA decrease (r = -0.363, P = 0.038). In PHI, sEPCR was stable (P = 0.35); there was a correlation between 48 week DD change and IL-6 change (r = +0.696, P = 0.0009) and also between 48 week DD change and sEPCR change (r = +0.553, P = 0.014). Despite the small sample size, we hypothesize that sEPCR levels reflect coagulant pathway activation caused by the endothelial damage during chronic infection more than a marker of the cytokine storm that occurs during PHI. Alternatively, in PHI, the link found between sEPCR and DD secondary to IL-6 suggests sEPCR is an indirect marker of inflammation.

摘要

背景

抗逆转录病毒疗法(ART)问世后,非艾滋病相关合并症成为 HIV 患者死亡的主要原因。多种生物标志物已被研究作为疾病的标志物。我们希望在 HIV 环境中检测可溶性内皮蛋白 C 受体(sEPCR)。

目的

主要目的是确定在接受 ART 治疗 48 周后,HIV 初治患者的 sEPCR 是否会降低。次要目的是比较慢性 HIV 感染(CHI)和原发性 HIV 感染(PHI)患者的 sEPCR 水平,并分析 sEPCR 是否与免疫病毒学参数以及不同的炎症标志物存在相关性。

患者和方法

我们分析了 33 名 CHI 初治患者和 19 名 PHI 初治患者的 sEPCR。sEPCR 与免疫病毒学参数(HIV RNA 和 CD4 细胞计数)以及白细胞介素 6(IL-6)或 D-二聚体(DD)进行了比较。

结果与结论

在 CHI 中,接受 ART 治疗 48 周后,sEPCR 显著降低(P=0.0006),基线 sEPCR 与 CD4 细胞增加(r=+0.463,P=0.007)和 HIV RNA 降低(r=-0.363,P=0.038)相关。在 PHI 中,sEPCR 保持稳定(P=0.35);48 周 DD 变化与 IL-6 变化之间存在相关性(r=+0.696,P=0.0009),48 周 DD 变化与 sEPCR 变化之间也存在相关性(r=+0.553,P=0.014)。尽管样本量较小,但我们假设 sEPCR 水平反映了慢性感染期间内皮损伤引起的凝血途径激活,而不是 PHI 期间发生的细胞因子风暴的标志物。或者,在 PHI 中,sEPCR 与 DD 之间发现的相关性继发于 IL-6,提示 sEPCR 是炎症的间接标志物。

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