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
| Autor: | Jeffrey L. Lennox, Kehmia Titanji, Neeta Shenvi, M. N. Weitzmann, Aswani Vunnava, Ighovwhera Ofotokun, Kirk A. Easley, Andrea Knezevic, Antonina Foster, Anandi N. Sheth |
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| Rok vydání: | 2018 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine medicine.medical_specialty Immunology Osteoporosis Bone resorption Flow cytometry 03 medical and health sciences 0302 clinical medicine Osteoprotegerin Internal medicine medicine Immunology and Allergy 030212 general & internal medicine medicine.diagnostic_test biology business.industry Activator (genetics) medicine.disease Osteopenia 030104 developmental biology Infectious Diseases Endocrinology RANKL biology.protein business Cytokine receptor |
| Zdroj: | AIDS. 32:885-894 |
| ISSN: | 0269-9370 |
| DOI: | 10.1097/qad.0000000000001764 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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