Influence of immune activation on the risk of allograft rejection in human immunodeficiency virus-infected kidney transplant recipients

Marco A. Lorio, Rossana Rosa, Jose F. Suarez, Phillip Ruiz, Gaetano Ciancio, George W Burke, Jose Camargo Galvis

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7 Citations (Scopus)

Abstract

Background 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. Methods 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. Results (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 3 years post-transplant compared to those in the higher activation tertile (36.9% vs. 0%; log-rank P = 0.04). Conclusions 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.

Original languageEnglish (US)
Pages (from-to)40-43
Number of pages4
JournalTransplant Immunology
Volume38
DOIs
StatePublished - Sep 1 2016

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Allografts
HIV
Transplants
Kidney
HLA-DR Antigens
Kidney Transplantation
HIV Infections
Immunosuppression
Flow Cytometry
Cohort Studies
Biomarkers
Transplant Recipients
T-Lymphocytes
Biopsy
Therapeutics

Keywords

  • Acute rejection
  • HIV
  • HLA-DR
  • Immune activation
  • Kidney transplant

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Transplantation

Cite this

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title = "Influence of immune activation on the risk of allograft rejection in human immunodeficiency virus-infected kidney transplant recipients",
abstract = "Background 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. Methods 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. Results (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 3 years post-transplant compared to those in the higher activation tertile (36.9{\%} vs. 0{\%}; log-rank P = 0.04). Conclusions 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.",
keywords = "Acute rejection, HIV, HLA-DR, Immune activation, Kidney transplant",
author = "Lorio, {Marco A.} and Rossana Rosa and Suarez, {Jose F.} and Phillip Ruiz and Gaetano Ciancio and Burke, {George W} and {Camargo Galvis}, Jose",
year = "2016",
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language = "English (US)",
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T1 - Influence of immune activation on the risk of allograft rejection in human immunodeficiency virus-infected kidney transplant recipients

AU - Lorio, Marco A.

AU - Rosa, Rossana

AU - Suarez, Jose F.

AU - Ruiz, Phillip

AU - Ciancio, Gaetano

AU - Burke, George W

AU - Camargo Galvis, Jose

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background 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. Methods 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. Results (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 3 years post-transplant compared to those in the higher activation tertile (36.9% vs. 0%; log-rank P = 0.04). Conclusions 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.

AB - Background 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. Methods 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. Results (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 3 years post-transplant compared to those in the higher activation tertile (36.9% vs. 0%; log-rank P = 0.04). Conclusions 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.

KW - Acute rejection

KW - HIV

KW - HLA-DR

KW - Immune activation

KW - Kidney transplant

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