Biomarkers of HIV associated malignancies and of drug interaction between anti-retrovirals (ARVs) and chemotherapy
Year: 2015
Type: dissertation
Study design: Observational Study
Abstract: INTRODUCTION: Altered immune mechanisms play a critical role in the pathogenesis of Non-Hodgkin lymphoma (NHL), as evidenced by increased rates of NHL among HIV+ patients [De Roos et al., 2012;Mellgren et al., 2012].AIMS: To determine whether biomarkers of B-, T-cell activation, and inflammation are elevated in HIV+NHL patients; and whether cART influences their expression.METHODS: The expression of CD8+CD38 and FoxP3 were determined by flow cytometry; the serum concentrations of circulating sCD20, sCD23, sCD27, sCD30 and sCD44 were determined by enzyme linked immunosorbent assay (ELISA); and the serum concentrations of circulating IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α were determined by meso-scale discovery (MSD) assay in 141 participants consisting of HIV positive NHL (HIV+NHL), HIV negative NHL (NHL); combination antiretroviral treated HIV+ (HIV+ cART), treatment naive HIV+ (cART-naïve HIV+) patients; and healthy controls.RESULTS: HIV+NHL patients had higher serum concentrations of sCD20 (p<0.0001 and p=0.0359), sCD23 (p=0.0192 and p<0.0001), sCD30 (p=0.0052 and p<0.0001), sCD44 (p=0.0014 and p<0.0001), and IL-4 (p=0.0234 and p=0.03360); and lower expression of FoxP3 (p<0.0001 and p=0.0171) as compared to NHL and HIV+ cART patients.As compared to NHL patients, the serum concentrations of IL-2 (p=0.0115), and TNF-α (p=0.0258) were higher in HIV+NHL patients, while those of IL-1β (p=0.0039) were significantly lower.HIV+NHL patients had higher expression of CD8+CD38 (p=0.0104),serum concentrations of IFN-γ (p=0.0085), and IL-6 (p=0.0265); and lower serum concentrations of IL-12p70 (p=0.0012)than HIV+ cART Stellenbosch University https://scholar.sun.ac.za iii patients.As compared to controls, NHL had higher concentrationsof all biomarkers investigated except FoxP3 expression.As compared to HIV+ cART and controls, cART-naïve HIV+ patients had higher concentrations of all biomarkers investigated except sCD23 and FoxP3 expression.CONCLUSION: Biomarkers of chronic B-and T-cell activation and inflammation are up-regulated in HIV+NHL and the untreated HIV+ state.cART decreases immune activation and inflammation.
Author: Thabile Brian Flepisi
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Harry Crossley Foundation
OpenAlex ID: W2279858070