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Country of residence is associated with distinct inflammatory biomarker signatures in HIV-infected patients.

ABSTRACT: BACKGROUND:Inflammation and coagulation biomarkers are independent predictors of morbidity and mortality in HIV-infected patients. The impact of country of residence on these biomarkers is unknown and was investigated in persons at similar stages of HIV infection. METHODS:Cryopreserved plasma specimens were analysed from 267 ART-naive patients with CD4 cell counts <100 cells/?l from Mexico (n=124) and South Africa (n=143). Biomarkers were compared and dimension reduction analyses were performed to highlight biosignatures according to nationality, gender and tuberculosis co-infection. RESULTS:Mexican patients were significantly different from South Africans with regard to age, gender, CD4 cell count, haemoglobin, presence of AIDS-defining illness and prevalence of active tuberculosis. After adjusting for baseline characteristics, patients from Mexico had higher levels of IFN-?, IL-8, and CXCL-10 whereas patients from South Africa had higher levels of fibrinogen, LTB4, P-selectin, protein S, and sCD40 ligand. The effect of country on the profile of biomarker expression was stronger than gender differences and tuberculosis co-infection. CONCLUSION:Inflammation and coagulation biomarkers vary significantly by country. Further studies are needed to evaluate how these differences may contribute to HIV pathogenesis and prognosis in diverse populations and how they can be accounted for in studies using biomarkers as surrogate end points.

SUBMITTER: Manion M

PROVIDER: S-EPMC5337418 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Country of residence is associated with distinct inflammatory biomarker signatures in HIV-infected patients.

Manion Maura M Andrade Bruno B BB DerSimonian Rebecca R Gu Wenjuan W Rupert Adam A Musselwhite Laura W LW Sierra-Madero Juan G JG Belaunzaran-Zamudio Pablo F PF Sanne Ian I Lederman Michael M MM Sereti Irini I

Journal of virus eradication 20170101 1

<h4>Background</h4>Inflammation and coagulation biomarkers are independent predictors of morbidity and mortality in HIV-infected patients. The impact of country of residence on these biomarkers is unknown and was investigated in persons at similar stages of HIV infection.<h4>Methods</h4>Cryopreserved plasma specimens were analysed from 267 ART-naive patients with CD4 cell counts <100 cells/μl from Mexico (<i>n</i>=124) and South Africa (<i>n</i>=143). Biomarkers were compared and dimension reduc ...[more]

PMID: 28275455

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Project description:Background:Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to their shared routes of transmission, approximately 10% of HIV-infected patients worldwide are chronically coinfected with HBV. Additionally, liver disease has become a major cause of morbidity and mortality in HBV/HIV coinfected patients due to prolonged survival with the success of antiretroviral therapy. The relationship between immune exhaustion markers (PD-1/PD-L1) and apoptotic markers such as Fas/FasL, TGF?1, TNF-?, and Th1/Th2 cytokines are not clearly delineated in HBV/HIV coinfection. Methods:Levels of soluble Fas/FasL, TGF?1, TNF-?, and sPD-1/sPD-L1 as well as Th1 and Th2 cytokines were evaluated in the sera of HBV-monoinfected (n = 30) and HBV/HIV-coinfected (n = 15) patients and compared to levels in healthy controls (n = 20). Results:HBV-monoinfected patients had significantly lower levels of the anti-inflammatory cytokine IL-4 (P < 0.05) and higher levels of apoptotic markers sFas, sFasL, and TGF?-1 (P < 0.001) compared to healthy controls. Coinfection with HIV was associated with higher levels of sFas, TNF-?, and sPD-L1 (P < 0.005), and higher levels of the pro-inflammatory cytokines IL-6, IL-8, and IL-12p70 (P < 0.05) compared to healthy controls. Patients with HBV infection had a unique biomarker clustering profile comprised of IFN-?, IL12p70, IL-10, IL-6, and TNF-? that was distinct from the profile of the healthy controls, and the unique HIV/HBV profile comprised GM-CSF, IL-4, IL-2, IFN-?, IL12p70, IL-7, IL-10, and IL-1?. In HBV monoinfection a significant correlation between sFasL and PD1(r = 0.46, P = < 0.05) and between sFas and PDL1 (r = 0.48, P = <0.01) was observed. Conclusion:HBV-infected and HBV/HIV-coinfected patients have unique apoptosis and inflammatory biomarker profiles that distinguish them from each other and healthy controls. The utilization of those unique biomarker profiles for monitoring disease progression or identifying individuals who may benefit from novel immunotherapies such as anti-PD-L1 or anti-PD-1 checkpoint inhibitors appears promising and warrants further investigation.

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Country of residence is associated with distinct inflammatory biomarker signatures in HIV-infected patients.

Publications

Country of residence is associated with distinct inflammatory biomarker signatures in HIV-infected patients.

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