The extent of HLA-DR expression on HLA-DR(+) Tregs allows the identification of patients with clinically relevant borderline rejection

Transpl Int. 2013 Mar;26(3):290-9. doi: 10.1111/tri.12032. Epub 2013 Jan 2.

Abstract

Regulatory T cells (Tregs) were shown to be involved into the pathogenesis of acute rejection after transplantation. The suppressive activity of the total regulatory T cell pool depends on its percentage of highly suppressive HLA-DR(+) -Treg cells. Therefore, both the suppressive activity of the total Treg pool and the extent of HLA-DR expression of HLA-DR(+) -Tregs (MFI HLA-DR) were estimated in non transplanted volunteers, patients with end-stage renal failure (ESRF), healthy renal transplant patients with suspicion on rejection, due to sole histological Bord-R or sole acute renal failure (ARF), and patients with clinically relevant borderline rejection (Bord-R and ARF). Compared to patients with only Bord-R or only ARF, the suppressive activity of the total Treg cell pool was exclusively reduced in patients with clinically relevant Bord-R. In parallel, the HLA-DR MFI of the DR(+) -Treg subset was significantly decreased in these patients, due to a significantly lower proportion of DR(high+) -Tregs, which were shown to have the highest suppressive capacity within the total Treg pool. Our findings clearly demonstrate that the determination of the HLA-DR MFI of the HLA-DR(+) -Treg subset allows a highly sensitive, specific and non-invasive discrimination between patients with clinically relevant Bord-R (Bord and ARF) and patients with subclinical rejection or other causes of transplant failure.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / analysis
  • Biopsy, Needle
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism
  • Graft Rejection / metabolism*
  • Graft Rejection / pathology
  • HLA-DR Antigens / immunology
  • HLA-DR Antigens / metabolism*
  • Humans
  • Immunohistochemistry
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / pathology
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / methods
  • Kidney Transplantation / mortality
  • Linear Models
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • ROC Curve
  • Reference Values
  • Risk Assessment
  • Sensitivity and Specificity
  • Survival Rate
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • Forkhead Transcription Factors
  • HLA-DR Antigens