Monitorización de las células T reguladoras circulantes en trasplante renal humano e influencia de la inmunosupresión farmacológica

Abstract

Introducción<br/>En la actualidad se buscan marcadores para identificar pacientes trasplantados que alcancen cierto grado de tolerancia. El más estudiado recientemente se engloba como células T reguladoras (Tregs), capaces de controlar la respuesta alogénica in vitro y con capacidad tolerogénica en modelos animales. En este trabajo se ha estudiado el comportamiento de Tregs en trasplantados renales y la implicación de procesos inflamatorios y fármacos inmunosupresores más comunes en estos pacientes. <br/>Material y Métodos<br/>Se midieron las Tregs sanguíneas en los pacientes trasplantados renales mediante citometría de flujo y su función in vitro en cultivos mixtos linfocitarios cada 6 meses post-trasplante hasta los 2 años. <br/>Resultados y conclusiones<br/>Los pacientes con enfermedad renal terminal presentan un número similar de Tregs que donantes sanos. A los 6 meses del trasplante se observa un descenso de Tregs, recuperándose posteriormente. Se observó una mayor frecuencia de Tregs en los pacientes tratados durante un año con inhibidores de mTOR que los tratados con inhibidores de calcineurina (CNI). Así mismo se observó cómo los niveles sanguíneos de los CNI tenían un efecto deletéreo sobre la función de las Tregs.

Introduction<br/>Kidney transplantation has become a therapeutic option choice in patients with chronic renal failure. With the advance of new immunosuppressive agents has been a lower incidence of acute rejection, but still persist long-term problems, largely associated with chronic treatment with immunosuppressive agents. Currently, are looking for markers to identify patients who reach a certain degree of tolerance in order to reduce immunosuppressive load avoiding side effects long term. The most studied biomarker in the last decade includes<br/>with the name of regulatory T cells (Tregs), these cells are able to control allogeneic response in vitro and has tolerogenic capacity demonstrated in many transplant models. Prior to validate this biomarker of transplant tolerance, this work has studied the behavior of Treg cells in renal transplant recipients and their coexistence in the most common inflammatory processes in these patients. In addition, we assess the role of drugs immunosuppressants on these cells.<br/><br/>Objectives<br/>Monitor the levels of Tregs in renal transplant patients and consider the involvement of different events inflammatory on the number of Tregs and to determine the involvement of different immunosuppressive treatments on the number and Tregs function.<br/><br/>Material and Methods<br/>There were two parallel studies, one prospective, in which Treg cells were measured in kidney transplants patients by flow cytometry and their<br/>function in vitro by mixed lymphocyte cultures. The samples were collected every 6 months post-transplant until 2 years. In another retrospective study enrolled 64 patients transplantation with a follow-up exceeding one year, divided<br/>in terms of maintenance therapy with calcineurin inhibitors (CNI) or mTOR inhibitors.<br/><br/>Results and conclusions <br/>At the time prior to transplantation, patients with ESRD have a similar number of Treg cells circulating than healthy donors, excluding retransplantated patients. At 6 months after transplantation there is a dramatic decrease in Treg cell numbers, when the immunosuppressive load is higher. Later the levels of Tregs were recovered. Within the immunosuppressive used in maintenance treatment, there was a higher frequency of Tregs in patients treated for one year with mTOR inhibitors when compared with patients received in the same period calcineurin inhibitors (CNI). Also it was observed that blood levels of the CNI had a deleterious effect on the function of Treg cells.