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Osteopenia and Osteoporosis in HIV-infected Patients Are Associated with Reduced Frequency of Central Memory CD8+CD127+ T Cells: T-cell activation/senescence associated with bone loss
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"the loss of CD127 in HIV/AIDS has been related to enhanced T cell activation/senescence, accelerated turnover and reduced function, our data suggest immune hyper-activation and T cell exhaustion as a pathogenetic pathway of HIV-related bone perturbations. Furthermore, our findings identify CD8+CD127+ as a novel feature of the HIV-associated bone metabolism disorders."
Reported by Jules Levin
CROI 2009 Montreal Feb 8-12
Lidia Gazzola*, P Cicconi, L Comi, M Casana, T Bini, L Pietrogrande, A D'Arminio Monforte, and G Marchetti
San Paolo Hosp, Milan, Italy
Background: HIV-infected patients are burdened by heightened prevalence of osteopenia or osteoporosis. Recently, much attention has been addressed to the role of T cell activation in the pathogenesis of bone metabolism disorders. Given the chronic immune hyper-activation in HIV/AIDS, we sought to address the possible association between osteopenia and osteoporosis in HIV+ patients and specific T cell immune-phenotypes in peripheral blood.
Methods: Bone density was measured by dual X-ray absorptiometry (DEXA) at the femoral neck and lumbar spine. Osteopenia and osteoporosis were respectively defined by a T score <-1 and <-2.5 (according to the World Health Organization). Patients with pathologic DEXA (PD) were compared to patients with normal DEXA (ND) in terms of demographics (age, sex, BMI), HIV-related parameters (AIDS, VL zenith, current CD4 and nadir, hepatitis co-infection, time on HAART); T-cell phenotype (CD8+CD38+, CD4+CD95+-CD8+CD95+, CD4+CD127+,CD8+CD127+, CD8+CD38+45R0+) and plasma levels of osteoclastogenic cytokines IL-7 and TNF-a (ELISA). Variables with p<0.05 were studied by multivariate linear regression.
Results:_Of the 78 patients we analyzed, 23 had normal DEXA (30%) and 55 pathologic DEXA (70%): osteopenia in 47 patients (60%) and osteoporosis in 8 patients (10%). pathologic DEXA and non-pathologic DEXA patients were comparable in terms of demographics and HIV-related parameters. T cell immune-phenotyping resulted in significantly lower mean CD8+CD127+ proportions in pathologic DEXA respect to non-pathologic DEXA patients (12.8%, IC95% 11.2 to 14.5%) vs 16.3%, IC95% 13.3 to 19.4%, p = 0.03), with no differences in any other phenotypes being observed. This result was confirmed by multivariate analysis, adjusted for demographics and HIV parameters: pathologic DEXA patients had lower mean CD8+CD127+ percentage, respect to non-pathologic DEXA patients (-4.2, IC95% -0.9 to -8, p = 0.03). To investigate whether plasma interleukin-7 (IL-7) might affect CD127 expression, we measured IL-7 and tumor necrosis factor-alpha (TNF-a) plasma levels. No differences in both cytokines were evidenced between 2 groups of patients.
Conclusions: Our data show lower mean frequency of central memory CD8+CD127+ in HIV+ patients with bone metabolism disorders, independently of demographic, HIV and HAART conditions. Given that the loss of CD127 in HIV/AIDS has been related to enhanced T cell activation/senescence, accelerated turnover and reduced function, our data suggest immune hyper-activation and T cell exhaustion as a pathogenetic pathway of HIV-related bone perturbations. Furthermore, our findings identify CD8+CD127+ as a novel feature of the HIV-associated bone metabolism disorders
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