Decreased levels of the serum inflammatory biomarkers, sGP130, IL-6, sCRP and BAFF, are associated with increased likelihood of AIDS related Kaposi's sarcoma in men who have sex with men.

Abstract

AIDS-related Kaposi's sarcoma (AIDS-KS) risk remains substantially elevated compared with the general population, even among patients who receive effective combination antiretroviral therapy. This study investigated the role of inflammatory and immune activating biomarkers in AIDS-KS in men who have sex with men in the Multicenter AIDS Cohort study between 1984 and 2010. Concentrations of 24 serum biomarkers; IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, sGP130, sIL-2Rα, sIL-6R, eotaxin, MCP-1, MCP4, MIP 1β, TARC, BLC-BCA1, IP-10, GM-CSF, IFN-γ, BAFF, sCD14, CD27, sTNFR-2, sCRP, and TNF-α were tested longitudinally in 1,501 men. The concentrations of each biomarker were compared between AIDS-KS cases and controls at multiple time points, 0-1 years, 1-2 years, 2-3 year, 3-5 years and over 5 years, prior to KS diagnosis or study termination, using univariate non-parametric Kruskal-Wallis tests and logistic regression, adjusted for HBV and HCV co-infection, race/ethnicity, age at last visit, education, smoking and CD4+ cell count. In univariate analyses, concentrations of four markers were consistently higher in cases; sIL-2Rα, IP-10, sTNFR-2, MCP-1, and five were higher in controls; GM-CSF, IL-6, MIP-1β, sCRP, sGP130. In the adjusted models concentrations of four markers were significantly inversely associated with AIDS-KS risk including sGP130 (OR=0.14, 95% CI = 0.03-0.73, BAFF (OR=0.60, 95% CI =0.16-0.90), sCRP (OR=0.61, 95% CI = 0.43-0.87) and IL-6 (OR=0.51, 95% CI = 0.35-0.76). These results support a role for markers of immune activation and inflammation in AIDS-KS and may highlight pathways to be targeted for risk stratification or therapeutics.