CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients.

Lemerle Lemerle,Subra Subra,Garnier Garnier,Croue Croue,Brilland Brilland,Duveau Duveau,Augusto Augusto,Blanchet Blanchet,Blanchard Blanchard,Planchais Planchais

doi:10.3390/jcm8081147

Abstract

Predictive biomarkers of acute rejection (AR) are lacking. Pre-transplant expression of CD45RC on blood CD8+ T cells has been shown to predict AR in kidney transplant (KT) patients. The objective of the present study was to study CD45RC expression in a large cohort of KT recipients exposed to modern immunosuppressive regimens. CD45RC expression on T cells was analyzed in 128 KT patients, where 31 patients developed AR, of which 24 were found to be T-cell mediated (TCMR). Pre-transplant CD4+ and CD8+ CR45RChigh T cell proportions were significantly higher in patients with AR. The frequency of CD45RChigh T cells was significantly associated with age at transplantation but was not significantly different according to gender, history of transplantation, pre-transplant immunization, and de novo donor specific anti-Human Leucocyte Antigen (HLA) antibody. Survival-free AR was significantly better in patients with CD8+ CD45RChigh T cells below 58.4% (p = 0.0005), but not different according to CD4+ T cells (p = 0.073). According to multivariate analysis, CD8+ CD45RChigh T cells above 58.4% increased the risk of AR 4-fold (HR 3.96, p = 0.003). Thus, pre-transplant CD45RC expression on CD8+ T cells predicted AR, mainly TCMR, in KT patients under modern immunosuppressive therapies. We suggest that CD45RC expression should be evaluated in a prospective study to validate its usefulness to quantify the pre-transplant risk of AR.

Highlights

Significant progress has been made over the past few years in the immunological and histological fields, allowing for better differentiation and to refine the diagnosis and prognosis of T cell-mediated rejection (TCMR) and of antibody-mediated rejection (ABMR) in kidney transplant patients [1]
We demonstrated in a previous work that the level of CD45RC expression at the surface of blood CD8+ T cells before kidney transplantation was associated with the risk of acute rejection (AR) after transplantation [10,13]
These results are in line with our previous work [10,13] and confirm the interest of CD45RC expression on T cells to assess the immunological risk of candidates to kidney transplantation

Summary

Introduction

Significant progress has been made over the past few years in the immunological and histological fields, allowing for better differentiation and to refine the diagnosis and prognosis of T cell-mediated rejection (TCMR) and of antibody-mediated rejection (ABMR) in kidney transplant patients [1]. While both rejection types may develop concomitantly, TCMR mainly occurs within the first year post-transplant, while ABMR usually develops later in the course and is associated with the presence of preformed or de novo donor-specific anti-Human Leucocyte Antigen (HLA) antibodies (DSA) [1,2]. The identification of patients with higher versus lower AR risk among low immunological risk patients would theoretically allow one to tailor the immunosuppressive regimen according to the AR risk and to decrease post-transplant morbidity [5,6]

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Conclusion