T-cell receptor activator of nuclear factor-kappa B ligand/osteoprotegerin imbalance is associated with HIV-induced bone loss in patients with higher CD4(+) T-cell counts

• Type of Material: Article
• Authors: Kehmia Titanji, Emory University; Aswani Vunnava, Emory University; Antonina Foster, Emory University; Anandi Sheth, Emory University; Jeffrey L Lennox, Emory University; Andrea Knezevic, Emory University; Neeta Shenvi, Emory University; Kirk Easley, Emory University; Ighovwerha Ofotokun, Emory University; M. Neale Weitzmann, Emory University
• Language: English
• Date: 2018-04-24
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
• Final Published Version (URL): https://insights.ovid.com/pubmed?pmid=29424771
• Title of Journal or Parent Work: AIDS
• ISSN: 0269-9370
• Volume: 32
• Issue: 7
• Start Page: 885
• End Page: 894
• Grant/Funding Information: The authors gratefully acknowledge services provided by the Emory Center for AIDS Research (CFAR) funded through NIADID (P30AI050409) ;and the Georgia Clinical and Translational Science Alliance (Georgia CTSA), funded through the National center for Advancing Translational Sciences (UL1TR002378).; K.T. is also supported by the National Heart, Lung and Blood Institute (NHLBI)(1K01HL131333).; Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health under Award Numbers R01AR059364, R01AR068157, and R01AR070091); and by the National Institute on Aging (NIA) under Award Number R01AG040013 to M.N.W. and I.O.; M.N.W. is also supported by a grant from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (5I01BX000105);and by NIAMS grant R01AR056090.
• Keywords: eceptor activator of nuclear factor-kappa B ligand; T cells; HIV-induced bone loss; osteoprotegerin; OSTEOCLAST FORMATION; MINERAL DENSITY; LYMPHOCYTES; Life Sciences & Biomedicine; IN-VITRO; Virology; RECOMMENDATIONS; LIGAND; DISEASE; INFECTION; bone loss; ANTIRETROVIRAL THERAPY; Science & Technology; Infectious Diseases; OSTEOPROTEGERIN; Immunology; HIV
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Public Health; Health Sciences, Immunology

Abstract

Objective: Higher incidence of osteopenia and osteoporosis underlie increased rates of fragility fracture in HIV infection. B cells are a major source of osteoprotegerin (OPG), an inhibitor of the key osteoclastogenic cytokine receptor activator of nuclear factor-κB ligand (RANKL). We previously showed that higher B-cell RANKL/OPG ratio contributes to HIV-induced bone loss. T-cell OPG production in humans, however, remains undefined and the contribution of T-cell OPG and RANKL to HIV-induced bone loss has not been explored. Design: We investigated T-cell OPG and RANKL production in ART-naive HIV-infected and uninfected individuals in relation to indices of bone loss in a cross-sectional study. Methods: T-cell RANKL and OPG production was determined by intracellular staining and flow cytometry, and plasma levels of bone resorption markers were determined by ELISA. Results: We demonstrate for the first time in-vivo human T-cell OPG production, which was significantly lower in HIV-infected individuals and was coupled with moderately higher T-cell RANKL production, resulting in a significantly higher T-cell RANKL/OPG ratio. T-cell RANKL/OPG ratio correlated significantly with BMD-derived z-scores at the hip, lumbar spine and femur neck in HIV-infected individuals with CD4+ T-cell counts at least 200 cells/μl but not in those with lower counts. Conclusion: Our data suggest that T cells may be a physiologically relevant source of OPG and T-cell RANKL/OPG imbalance is associated with HIV-induced bone loss in CD4+ T-cell-sufficient patients. Both B and T lymphocytes may thus contribute to HIV-induced bone loss.