1.
Plasma soluble CD163 is associated with postmortem brain pathology in human immunodeficiency virus infection.
Bryant, AK, Moore, DJ, Burdo, TH, Lakritz, JR, Gouaux, B, Soontornniyomkij, V, Achim, CL, Masliah, E, Grant, I, Levine, AJ, et al
AIDS (London, England). 2017;(7):973-979
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Abstract
OBJECTIVE Higher plasma soluble cluster of differentiation (CD)163 (sCD163), shed by monocytes and macrophages, correlates with neurocognitive impairment in HIV infection. We hypothesized that higher antemortem plasma or cerebrospinal fluid (CSF) sCD163 would be associated with greater postmortem neurodegeneration and/or microgliosis. DESIGN Retrospective, postmortem observational study. METHODS We measured sCD163 levels in antemortem plasma (n = 54) and CSF (n = 32) samples from 74 HIV-seropositive participants (median 5 months before death) who donated their brains to research at autopsy. Postmortem, we quantified markers of synaptodendritic damage (microtubule-associated protein 2, synaptophysin), microgliosis [human leukocyte antigen DR (HLA-DR), ionized calcium-binding adaptor molecule 1], astrocytosis (glial fibrillary acidic protein), and impaired protein clearance (β-amyloid) in frontal cortex, hippocampus, putamen, and internal capsule. Multivariable least-squares regression was used to evaluate the association between plasma or CSF sCD163 and histological measures, correcting for multiple comparisons. RESULTS Higher plasma sCD163 was associated with lower microtubule-associated protein 2 in frontal cortex [B = -0.23, 95% confidence interval (CI) -0.41 to -0.06, P = 0.04], putamen (B = 0.32, 95% CI -0.52 to -0.12, P = 0.02), and hippocampus (B = -0.23, 95% CI -0.35 to -0.10, P = 0.01), and with lower synaptophysin in hippocampus (B = -0.25, 95% CI -0.42 to -0.03, P = 0.02) but not putamen or frontal cortex (P > 0.05). Higher plasma sCD163 was associated with higher HLA-DR in putamen (B = 0.17, 95% CI 0.08 to 0.26, P = 0.008). CSF sCD163 was not associated with any histological measure (P > 0.05). CONCLUSION Higher plasma sCD163 in life is associated with greater synaptodendritic damage and microglial activation in cortical and subcortical brain regions.
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The association of high sCD163/sTWEAK ratio with cardiovascular disease in hemodialysis patients.
Rusu, CC, Racasan, S, Kacso, IM, Ghervan, L, Moldovan, D, Potra, A, Patiu, IM, Bondor, C, Caprioara, MG
International urology and nephrology. 2015;(12):2023-30
Abstract
PURPOSE Cardiovascular disease (CVD) is the most common cause of death in hemodialysis (HD) patients. Transmembrane proteins that circulate as soluble form such as tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and CD163 have been proposed in previous studies as CVD biomarkers in chronic kidney disease patients. In HD patients, since studies are scarce, the role of these proteins is not completely understood. We tested the hypothesis that sTWEAK, sCD163 or sCD163/sTWEAK ratio could be associated with cardiovascular disease in HD patients. METHODS We recorded current clinical and biological data, and we measured sTWEAK and sCD163 serum levels by ELISA in 70 hemodialysis patients. Univariate analysis and multivariate (logistic regression) analysis were used to identify the relation between sTWEAK, sCD163 and sCD163/sTWEAK ratio and CVD. RESULTS In univariate analysis, CVD in HD patients is associated with higher sCD163/sTWEAK ratio (p = 0.04), sCD163 (p = 0.07), CRP (p = 0.04), age (p = 0.07), smoking (p = 0.09) and vascular calcifications (p = 0.10). In multivariate analysis, only logarithm of sCD163/sTWEAK ratio (p = 0.04) and smoking (p = 0.03) was significantly associated with CVD. The levels of these molecules and their ratio were correlated with atherosclerosis risk factors: diabetes mellitus, high fasting glucose, tricipital skinfold thickness and CRP as well as (for sCD163/sTWEAK) intravenous iron therapy. CONCLUSIONS Cardiovascular disease is associated with increased sCD163/sTWEAK ratio. To our knowledge, this is the first report about this relationship in HD patients.