Abstract
Chronic inflammation and B-cell hyperactivation are seen in HIV infection, contributing to an increased risk for the accrual of genetic errors that may result in B-cell lymphoma. The primary objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) on serum levels of molecules that are associated with immune activation and/or inflammation, including several that are associated with B-cell activation, specifically IL-6, sCD30, sCD27, IgG, IgA, CXCL13 (B lymphocyte chemoattractant, BLC), a B-lymphocyte chemokine involved in B-cell trafficking, as well as C-reactive protein, an acute-phase protein. We used a retrospective cohort study design, measuring serum levels of these markers at each of four 1-year intervals, 2 years before and 2 years after HAART initiation, in a subgroup of 290 HIV-infected men enrolled in the Multicenter AIDS Cohort Study (MACS). Serum levels of immune activation-associated molecules were measured by ELISA and multiplexed immunometric assays. Reference values were determined by the 5th to 95th percentiles from a sample of 109 HIV-uninfected MACS men. HAART use was associated with a reduction, but not normalization, of most biomarkers tested. Serum levels of IL-6 and C-reactive protein appeared to be unaffected by HAART. These results suggest a partial normalization of serum cytokine levels post HAART. However, a chronic state of B-cell hyperactivation continues 2-3 years after HAART initiation. These findings may explain, in part, the excess incidence of lymphoma still occurring in HIV-infected persons in the post-HAART era.
Highlights
With HIV infection, there is a quantitative decrease and dysfunction of T-lymphocyte (T cell) activity, as well as an increase in B-cell activation [1,2,3] and an overproduction of Blymphocyte (B cell) stimulatory cytokines [4,5,6]
Serum levels of interleukin 6 (IL-6) and C-reactive protein appeared to be unaffected by highly active antiretroviral therapy (HAART)
A chronic state of B-cell hyperactivation continues 2–3 years after HAART initiation. These findings may explain, in part, the excess incidence of lymphoma still occurring in HIV-infected persons in the post-HAART era
Summary
With HIV infection, there is a quantitative decrease and dysfunction of T-lymphocyte (T cell) activity, as well as an increase in B-cell activation [1,2,3] and an overproduction of Blymphocyte (B cell) stimulatory cytokines [4,5,6]. Progressive increases in levels of many of these molecules are seen as persons progress to AIDS, and even higher levels in those who develop AIDS-related non-Hodgkin lymphoma (AIDS-NHL) [13, 14, 16,17,18,19,20,21,22,23,24] In addition to their effects in promoting B-cell activation, many of these cytokines and immune stimulatory molecules have broader effects, and can promote inflammation and contribute to generalized immune system activation. Interleukin 6 (IL-6) is a proinflammatory cytokine with pleitropic biological effects, in addition to being a potent B-cell-stimulatory cytokine [25, 26]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
