High Proportion of Pretransplantation Activated Regulatory T cells (CD4+CD25highCD62L+CD45RO+) Predicts Acute Rejection in Kidney Transplantation: Results of a Multicenter Study

Background. Prognostic biomarkers of acute rejection (AR) in solid organ transplantation have been addressed in multiple small retrospective studies, and there is a critical need for multicenter studies. Because of their tolerogenic properties, regulatory T cells (Tregs) play an important role in transplant outcome. Methods. In the present multicenter study, we have retrospectively examined different Treg subpopulations in an independent cohort of kidney transplant patients within first year after kidney transplantation. All participating centers used identical flow cytometry standard operating procedures. Results. Seventy-five renal transplant patients were included, and six of them experienced an AR episode. The activated Treg (aTreg) subpopulation (CD4(+)CD25(high)CD62L(+)CD45RO(+)) was increased in the AR group before transplantation, and an aTreg percentage higher than 1.46% before kidney transplantation conferred an increased risk of AR. The univariate logistic regression model achieved an area under the curve of 81.6%. By including recipient age and thymoglobulin induction as variables in a multivariate logistic regression model, the prediction of AR improved to 92.4%. Conclusion. The evaluation of CD4(+)CD25(high)CD62L(+)CD45RO(+) aTreg cells may be useful as pretransplantation predictive biomarker of AR in kidney transplant patients. Definitive confirmation of our results awaits tests in validation groups.