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Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors.

ABSTRACT: We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile) and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p<0.001), sCD163 was significantly reduced among 'aviraemic' patients only (p = 0.02), while sCD14 was unaffected by virological status under 10,000 copies/mL (p>0.2). Associations between higher sCD163 and protease inhibitor therapy (p = 0.05) and lower sCD14 with integrase inhibitor therapy (p = 0.02) were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI), with a favourable influence of Framingham score <10% (p = 0.04). Soluble CD14 levels were higher among smokers (p = 0.002), with no effect of other CVD risk factors, except age (p = 0.045). Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation.

SUBMITTER: Castley A

PROVIDER: S-EPMC4927121 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors.

Castley Alison A Williams Leah L James Ian I Guelfi George G Berry Cassandra C Nolan David D

PloS one 20160629 6

We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profil ...[more]

PMID: 27355513

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Project description:BackgroundEmerging evidence argues that monocytes, circulating innate immune cells, are principal players in COVID-19 pneumonia. The study aimed to investigate the role of soluble (s)CD163 and sCD14 plasmatic levels in predicting disease severity and characterize peripheral blood monocytes and dendritic cells (DCs), in patients with COVID-19 pneumonia (COVID-19 subjects).MethodsOn admission, in COVID-19 subjects sCD163 and sCD14 plasmatic levels, and peripheral blood monocyte and DC subsets were compared to healthy donors (HDs). According to clinical outcome, COVID-19 subjects were divided into ARDS and non-ARDS groups.ResultsCompared to HDs, COVID-19 subjects showed higher sCD163 (p<0.0001) and sCD14 (p<0.0001) plasmatic levels. We observed higher sCD163 plasmatic levels in the ARDS group compared to the non-ARDS one (p=0.002). The cut-off for sCD163 plasmatic level greater than 2032 ng/ml was predictive of disease severity (AUC: 0.6786, p=0.0022; sensitivity 56.7% [CI: 44.1-68.4] specificity 73.8% [CI: 58.9-84.7]). Positive correlation between plasmatic levels of sCD163, LDH and IL-6 and between plasmatic levels of sCD14, D-dimer and ferritin were found. Compared to HDs, COVID-19 subjects showed lower percentages of non-classical (p=0.0012) and intermediate monocytes (p=0.0447), slanDCs (p<0.0001), myeloid DCs (mDCs, p<0.0001), and plasmacytoid DCs (pDCs, p=0.0014). Compared to the non-ARDS group, the ARDS group showed lower percentages of non-classical monocytes (p=0.0006), mDCs (p=0.0346), and pDCs (p=0.0492).ConclusionsThe increase in sCD163 and sCD14 plasmatic levels, observed on hospital admission in COVID-19 subjects, especially in those who developed ARDS, and the correlations of these monocyte/macrophage activation markers with typical inflammatory markers of COVID-19 pneumonia, underline their potential use to assess the risk of progression of the disease. In an early stage of the disease, the assessment of sCD163 plasmatic levels could have clinical utility in predicting the severity of COVID-19 pneumonia.

Project description:The risk factors for cerebral malaria (CM) and the wide variation in clinical manifestations of malaria are poorly understood. Recent studies indicate that interferon gamma inducible chemokine, CXCL10, is a strong predictor of both human and experimental cerebral malaria. Increased plasma and cerebrospinal fluid levels of CXCL10 were tightly associated with fatal CM in Indian and Ghanaian patients. In the present study, we hypothesized that in a subset of malaria patients, CM susceptibility is associated with variation in CXCL10 expression. We determined whether polymorphisms in the CXCL10 gene promoter region played a role in the clinical status of malaria patients and addressed the genetic basis of CXCL10 expression during malaria infection. Following extensive bioinformatics analyses, two reported single nucleotide polymorphisms in the CXCL10 promoter (-135G>A [rs56061981] and -1447A>G [rs4508917]) were identified among 66 CM and 69 non-CM Indian patients using PCR-restriction fragment length polymorphism assay. Individuals with the -1447(A/G) genotype were susceptible to CM (adjusted odds ratio [AOR] = 2.60, 95% CI = 1.51-5.85, p = 0.021). In addition, individuals with the -1447(A/G) genotype had significantly higher plasma CXCL10 levels than individuals with the -1447(A/A) genotype. Stratifying patients according to gender, the observed association of CM with over expression of CXCL10 were more pronounced in males than in female patients (AOR = 5.47, 95% CI = 1.34-22.29, p = 0.018). Furthermore, -135G>A polymorphism conferred a decreased risk of CM among males (AOR = 0.19, 95% CI = 0.05-0.78, p = 0.021). Polymorphisms in the CXCL10 gene promoter sequence were associated with increased CXCL10 production, which is linked to severity of CM. These results suggest that the -1447A>G polymorphism in CXCL10 gene promoter could be partly responsible for the reported variation underlying severity of CM outcomes particularly in males.

Project description:Abstract Background Both antiretroviral therapy (ART) and polymorphism in genes involved in lipoprotein metabolism contribute to the development of ART-induced dyslipidemia. Apolipoprotein A5 (APOA5)gene variant, which vary by race/ethnicity, influence plasma lipid concentrations. We explored the association of candidate gene effect on plasma lipid levels with food in HIV-infected children initiating ART in south India. Methods HIV-infected children, between 2 and 12 years of age initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART during 2010–2014 were included. They were assessed for their dietary intake by 24-hour dietary recall. Fasting blood was drawn for serum triglycerides (TGL), total cholesterol and high-density cholesterol along with CD4 cell count, and HIV-1 viral load. APOA5 gene polymorphisms rs662799, rs3135506 were determined by Taqman single-nucleotide polymorphism (SNP) genotyping assays. The General Linear Model (GLM) was applied to explore the risk of hypertriglyceridemia for SNP’s rs662799 and rs3135506 with food interaction in children. Results Three hundred and ninety HIV-infected children {median age (IQR): 9 (5–11) years; and median viral load: 141,000 (25,876–436,000) copies/mL} were started on NNRTI-based ART. The frequency of c allele was 20% and 3.0% in rs662799, rs3135506, respectively. The GLM model suggested that the SNP rs662799 has significant association with TGL(P < 0.01); there was, however no interaction between gene polymorphisms and food. Also, the prediction model revealed that those who had a carrier allele (C) had higher TGL level as compared with those with wild type (165 vs. 138 mg/dL) and girls had higher TGL levels compared with boys. Conclusion Children with carrier allele of APOA5 are prone to hypertriglyceridemia, irrespective of diet or drugs. These children require periodic monitoring of lipid parameters and effective interventions to prevent the development of atherogenic or metabolic complications. Disclosures All authors: No reported disclosures.

Dataset Information

Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors.

Publications

Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors.

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