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

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⁺ CR45RC^high T cell proportions were significantly higher in patients with AR. The frequency of CD45RC^high 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⁺ CD45RC^high T cells below 58.4% (p = 0.0005), but not different according to CD4⁺ T cells (p = 0.073). According to multivariate analysis, CD8⁺ CD45RC^high 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.

Keywords: CD45RC; acute rejection; kidney transplantation; lymphocyte.

Figure 1

Flowchart of the study.

Figure 2

Analysis of proliferative capacities of CD45RC^low and CD45RC^high T cells in ESRD patients and HD. After 72 h, the proliferation of activated CD4⁺CD45RC^low (A), CD4⁺CD45RC^high (B), CD8⁺CD45RC^low (C), and CD8⁺CD45RC^high (D) T cell subsets of ESRD patients (black bars) and HD (white bars) was analyzed. The experiment reported results of four ESRD patients and four age and matched HD. Error bars show the median with a 95% CI. Comparisons were done using the Wilcoxon matched-pairs rank test. ns, non-significant. CI, Confidence Interval; ESRD: end-stage renal disease; HD: heathy individuals.

Figure 3

Proportion of CD45RC^high and CD45RC^low CD4+ and CD8+ T cells according to gender (A), previous transplantation (B), pre-transplant PRA (C), de novo DSA occurrence (D), and age at transplantation (E). For A–D, comparisons were done using the Mann–Whitney U test and error bars show median with a 95% CI. For E, correlation analysis was done using the Spearman test. CI, Confidence Interval; PRA, Panel Reactive Antibody.

Figure 4

Predictive value of CD4⁺ and CD8⁺ CD45RC T cell subsets. (A) ROC curve analysis of CD4⁺ and CD8⁺ CD45RC^high T cell subsets for AR prediction. (B) Rejection-free survival of patients according to CD8⁺ (upper panel) and CD4⁺ CD45RC^high T cell proportions. Comparison between survivals was done using a log-rank test. (C) predictive values of CD8⁺ CD45RC^high T cell above 58.4% for AR prediction. AUC: Area Under Curve.