| Autor: |
TITANJI, Kehmia, VUNNAVA, Aswani, FOSTER, Antonina, SHETH, Anandi N., LENNOX, Jeffrey L., KNEZEVIC, Andrea, SHENVI, Neeta, EASLEY, Kirk A., OFOTOKUN, Ighovwerha, WEITZMANN, M. Neale |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
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| 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-naïve 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 ≥ 200 cells/μl but not in those with lower counts. CONCLUSIONS: 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 |
| Externí odkaz: |
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