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T-cell receptor activator of nuclear factor-κB ligand/osteoprotegerin imbalance is associated with HIV-induced bone loss in patients with higher CD4+ T-cell counts.
- Source :
-
AIDS (London, England) [AIDS] 2018 Apr 24; Vol. 32 (7), pp. 885-894. - Publication Year :
- 2018
-
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.<br />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.<br />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.<br />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.<br />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.
Details
- Language :
- English
- ISSN :
- 1473-5571
- Volume :
- 32
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- AIDS (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 29424771
- Full Text :
- https://doi.org/10.1097/QAD.0000000000001764