Kirkegaard-Klitbo Ditte M, Mejer Niels, Knudsen Troels B, Møller Holger J, Moestrup Søren K, Poulsen Susanne D, Kronborg Gitte, Benfield Thomas
aDepartment of Infectious Diseases, Hvidovre Hospital bDepartment of Infectious Diseases, Rigshospitalet cDepartment of Pulmonary and Infectious Diseases, Hillerød Hospital, University of Copenhagen, Copenhagen dDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus eDepartment of Molecular Medicine, University of Southern Denmark, Odense fDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
AIDS. 2017 Apr 24;31(7):981-988. doi: 10.1097/QAD.0000000000001432.
To examine if monocyte and macrophage activity may be on the mechanistic pathway to non-AIDS comorbidity by investigating the associations between plasma-soluble CD163 (sCD163) and incident non-AIDS comorbidities in well treated HIV-infected individuals.
Prospective single-center cohort study.
Plasma sCD163 was quantified by ELISA technique at study entry in 2004/2005, and non-AIDS comorbidity was identified by International Classification of Disease Tenth revision diagnosis codes and registry linkage in 2015. Associations between sCD163 and incident comorbidity was examined using multivariable Cox proportional hazards models adjusted for pertinent covariates.
In HIV-1-infected individuals (n = 799), the highest quartile of plasma sCD163 was associated with incident chronic lung disease [adjusted hazard ratio (aHR), 3.2; 95% confidence interval (CI): 1.34; 7.46] and incident chronic kidney disease (aHR, 10.94; 95% CI: 2.32; 51.35), when compared with lowest quartiles. Further, (every 1 mg) increase in plasma sCD163 was positively correlated with incident liver disease (aHR, 1.12; 95% CI: 1.05; 1.19). The sCD163 level was not associated with incident cancer, cardiovascular disease or diabetes mellitus.
sCD163 was independently associated with incident chronic kidney disease, chronic lung disease and liver disease in treated HIV-1-infected individuals, suggesting that monocyte/macrophage activation may be involved in the pathogenesis of non-AIDS comorbidity and a potential target for therapeutic intervention.
通过研究血浆可溶性CD163(sCD163)与接受良好治疗的HIV感染个体发生非艾滋病合并症之间的关联,来检验单核细胞和巨噬细胞活性是否可能处于非艾滋病合并症的发病机制途径上。
前瞻性单中心队列研究。
2004/2005年研究开始时通过ELISA技术对血浆sCD163进行定量,2015年通过国际疾病分类第十次修订诊断编码和登记联动来确定非艾滋病合并症。使用针对相关协变量进行调整的多变量Cox比例风险模型来检验sCD163与新发合并症之间的关联。
在HIV-1感染个体(n = 799)中,与最低四分位数相比,血浆sCD163的最高四分位数与新发慢性肺病[调整后风险比(aHR),3.2;95%置信区间(CI):1.34;7.46]和新发慢性肾病(aHR,10.94;95%CI:2.32;51.35)相关。此外,血浆sCD163每增加(1毫克)与新发肝病呈正相关(aHR,1.12;95%CI:1.05;1.19)。sCD163水平与新发癌症、心血管疾病或糖尿病无关。
在接受治疗的HIV-1感染个体中,sCD163与新发慢性肾病、慢性肺病和肝病独立相关,表明单核细胞/巨噬细胞激活可能参与非艾滋病合并症的发病机制,并且是治疗干预的潜在靶点。