title: Association between peripheral T-Lymphocyte activation and impaired bone mineral density in HIV-infected patients.
abstract: BACKGROUND
  HIV-infected patients display an increased and early incidence of osteopenia/osteoporosis. We investigated whether bone metabolism disorders in HIV-infected patients are related to immune hyperactivation and premature immune senescence.
  
  
  METHODS
  Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA): low BMD (LBMD) was defined as T-score or z-score < -1. CD4+/CD8+ phenotype (CD38/HLA-DR, CD127, CD28/CD57), and circulating IL-7, TNF-α, RANKL, OPG were measured. The variables with p < .05 were evaluated by multivariate logistic regression.
  
  
  RESULTS
  78 patients were enrolled: 55 were LBMD. LBMD patients showed increased activated HDLADR + CD4+ and CD8+ (p = .03 and p = .002, respectively). Interestingly, no differences in senescent CD28-CD57 + CD4+/CD8+ T-cells were observed between groups. However, LBMD patients displayed a decreased CD4 + CD28- phenotype (p = .04) at the advantage of the CD28+ pool (p = .03), possibly reflecting heightened apoptosis of highly differentiated CD28-negative cells.Activated HLADR + CD4+/CD8+ and CD28 + CD4+ cells were independently associated with impaired BMD (AOR = 1.08 for each additional HLADR + CD4+ percentage higher; CI 95%,1.01-1.15; p = .02; AOR = 1.07 for each additional HLADR + CD8+ percentage higher; CI 95%,1.01-1.11; p = .01; AOR = 1.06 for each additional CD28 + CD4+ percentage higher; CI 95%,1.0-1.13; p = .05).
  
  
  CONCLUSIONS
  Heightened T-cell activation in HIV-infected patients independently predicts BMD disorders, suggesting a critical role of immune activation in the pathogenesis of osteopenia/osteoporosis, even in patients achieving full viral suppression with HAART.
authors: Department of Health Sciences, Clinic of Infectious Diseases, San Paolo Hospital, University of Milan, Via A, Di Rudinì, 8, Milan 20142, Italy.
authors: Lidia
authors: L
authors: Gazzola
authors: Giusi Maria
authors: GM
authors: Bellistri
authors: Camilla
authors: C
authors: Tincati
authors: Valentina
authors: V
authors: Ierardi
authors: Alessia
authors: A
authors: Savoldi
authors: Angelo
authors: A
authors: Del Sole
authors: Luca
authors: L
authors: Tagliabue
authors: Antonella
authors: A
authors: d'Arminio Monforte
authors: Giulia
authors: G
authors: Marchetti
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D015519:Bone Density; D016516:CD4-CD8 Ratio; D016207:Cytokines / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines