Soluble CD163, a Novel Marker of Activated Macrophages, Is Elevated and Associated With Noncalcified Coronary Plaque in HIV-Infected Patients

Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 10/2011; 204(8):1227-36. DOI: 10.1093/infdis/jir520
Source: PubMed


Pro-inflammatory monocytes/macrophages may contribute to increased atherosclerosis in human immunodeficiency virus (HIV)-infected patients. We investigate--to our knowledge, for the first time--sCD163 and other markers of monocyte activation in relationship to atherosclerotic plaque in HIV-infected patients.
One hundred two HIV-infected and 41 HIV-seronegative men with equivalent cardiovascular risk factors and without history of coronary artery disease were prospectively recruited and underwent computed tomography coronary angiography.
sCD163 levels and presence of plaque were significantly higher among antiretroviral-treated subjects with undetectable HIV RNA levels, compared with seronegative controls (1172 ± 646 vs. 883 ± 561 ng/mL [P = .02] for sCD163 and 61% vs. 39% [P = .03] for presence of plaque). After adjusting for age, race, lipids, blood pressure, glucose, smoking, sCD14, and HIV infection, sCD163 remained independently associated with noncalcified plaque (P = .008). Among HIV-infected patients, sCD163 was associated with coronary segments with noncalcified plaque (r = 0.21; P = .04), but not with calcium score. In contrast, markers of generalized inflammation, including C-reactive protein level, and D-dimer were not associated with sCD163 or plaque among HIV-infected patients.
sCD163, a monocyte/macrophage activation marker, is increased in association with noncalcified coronary plaque in men with chronic HIV infection and low or undetectable viremia. These data suggest a potentially important role of chronic monocyte/macrophage activation in the development of noncalcified vulnerable plaque.

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    • "The frequency of inflammatory CD16+ monocytes is associated with risk of coronary artery progression [20]. Soluble CD14 was reported to be an independent predictor of mortality in HIV [21] and has been related to the increase in the yearly rate of carotid intima-media thickness [22], whereas soluble CD163 has been associated with increased risk of coronary artery inflammation and atherosclerosis and with subclinical atherosclerosis [23]. In addition, a study that assessed neurocognitive impairment in virologically suppressed HIV patients found higher levels of soluble CD163 in patients with a higher global deficit score, suggesting persistent monocyte activation in neuropsychological impaired patients [24]. "
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    ABSTRACT: Introduction Monotherapy with protease-inhibitors (MPI) may be an alternative to cART for HIV treatment. We assessed the impact of this strategy on immune activation, bacterial translocation and inflammation. Methods We performed a cross-sectional study comparing patients on successful MPI (n=40) with patients on cART (n=20). Activation, senescence, exhaustion and differentiation stage in CD4+ and CD8+ T lymphocyte subsets, markers of monocyte activation, microbial translocation, inflammation, coagulation and low-level viremia were assessed. Results CD4+ or CD8+ T lymphocyte subset parameters were not significantly different between both groups. Conversely, as compared with triple cART, MPI patients showed a higher proportion of activated monocytes (CD14+ CD16−CD163+ cells, p=0.031), soluble markers of monocyte activation (sCD14 p=0.004, sCD163 p=0.002), microbial translocation (lipopolysaccharide (LPS)-binding protein; LBP p=0.07), inflammation (IL-6 p=0.04) and low-level viremia (p=0.035). In a multivariate model, a higher level of CD14+ CD16−CD163+ cells and sCD14, and presence of very low-level viremia were independently associated with MPI. Monocyte activation was independently associated with markers of inflammation (IL-6, p=0.006), microbial translocation (LBP, p=0.01) and low-level viremia (p=0.01). Conclusions Patients on MPI showed a higher level of monocyte activation than patients on standard therapy. Microbial translocation and low-level viremia were associated with the high level of monocyte activation observed in patients on MPI. The long-term clinical consequences of these findings should be assessed.
    Journal of the International AIDS Society 09/2014; 17(1):19246. DOI:10.7448/IAS.17.1.19246 · 5.09 Impact Factor
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    • "Elevated levels of sCD163 are observed in several comorbidities associated with cART-treated HIV infection. Plasma sCD163 is associated with an increased prevalence of atherosclerotic plaques in cART-treated HIV-infected persons with undetectable HIV RNA, a relationship that is not observed in HIV-negative controls matched for cardiovascular risk factors [90]. The authors suggest that activation of mononuclear phagocytes during HIV infection could cause a unique atherosclerotic plaque phenotype not observed in HIV-uninfected persons. "
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    ABSTRACT: Combined antiretroviral therapy (cART) extends the lifespan and the quality of life for HIV-infected persons but does not completely eliminate chronic immune activation and inflammation. The low level of chronic immune activation persisting during cART-treated HIV infection is associated with the development of diseases which usually occur in the elderly. Although T-cell activation has been extensively examined in the context of cART-treated HIV infection, monocyte activation is only beginning to be recognized as an important source of inflammation in this context. Here we examine markers and sources of monocyte activation during cART-treated HIV infection and discuss the role of monocytes during cardiovascular disease, HIV-associated neurocognitive disorder, and innate immune aging.
    Research Journal of Immunology 06/2014; 2014:569819. DOI:10.1155/2014/569819
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    • "Additionally, in early diagnosed HIV patients, the sCD163 concentration returned to levels observed in HIV-seronegative individuals [30]. Higher levels of sCD163 in HIV-infected patients with ART have also been reported in some but not all studies [31], [46]. "
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    ABSTRACT: Patients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV. The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII) and endothelial dysfunction (sVCAM-1 and ADMA) in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART) and 23 healthy subjects. Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations. HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART.
    PLoS ONE 03/2014; 9(3):e90541. DOI:10.1371/journal.pone.0090541 · 3.23 Impact Factor
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