Influence of immune activation on the risk of allograft rejection in human immunodeficiency virus-infected kidney transplant recipients.
HIV infection is associated with high rates of acute rejection following kidney transplantation. The underlying mechanisms for such predisposition are incompletely understood. Pathological immune activation is a hallmark of chronic HIV infection that persists despite effective antiretroviral therapy. We hypothesized that the baseline levels of T cell activation in HIV(+) candidates would correlate with their risk of acute rejection following kidney transplantation.



Single-center retrospective cohort analysis of HIV(+) adult kidney transplants performed between October 2006 and September 2013. The frequency of CD3(+)HLA-DR(+) cells measured by flow cytometry served as a surrogate marker of immune activation. Patients were categorized into tertiles of activation, and the rates of biopsy-proven acute rejection were compared across groups.



(1) Compared to matched HIV(-) controls, the baseline number of CD3(+)HLA-DR(+) cells was higher in HIV(+) kidney transplant candidates. (2) Abnormally high levels of activation did not decrease with transplant-associated immunosuppression. (3) Patients categorized within the lower and middle CD3(+)HLA-DR(+) tertiles had higher probability of rejection during the first 3years post-transplant compared to those in the higher activation tertile (36.9% vs. 0%; log-rank P=0.04).



Pathological immune activation in HIV(+) transplant candidates does not explain their increased susceptibility to allograft rejection. Paradoxically, those with the highest levels of immune activation seem to be less prone to rejection.
Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
Marco A
MA
Lorio
Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, USA.
Rossana
R
Rosa
Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
Jose F
JF
Suarez
Department of Surgery, University of Miami Miller School of Medicine and Miami Transplant Institute at the Jackson Memorial Hospital, Miami, FL, USA.
Phillip
P
Ruiz
Department of Surgery, University of Miami Miller School of Medicine and Miami Transplant Institute at the Jackson Memorial Hospital, Miami, FL, USA.
Gaetano
G
Ciancio
Department of Surgery, University of Miami Miller School of Medicine and Miami Transplant Institute at the Jackson Memorial Hospital, Miami, FL, USA.
George W
GW
Burke
Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, USA.
Jose F
JF
Camargo
D000208:Acute Disease; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology*; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012306:Risk; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous; D014481:United States / Q000453:epidemiology
D006684:HLA-DR Antigens
Acute rejection; HIV; HLA-DR; Immune activation; Kidney transplant