Kinetics of anti- HLA antibodies and regulatory cells in kidney transplantation: impact on acute rejection and chronic graft loss

Abstract

Kidney transplantation is currently the preferred therapy for most patients with chronic renal failure. Despite the substantial improvement in renal graft survival in recent decades, chronic rejection and antibody-mediated rejection remain major problems.There are consistent data in the literature showing a strong association between the detection of anti-HLA alloantibodies and the greater frequency and severity of acute and chronic rejection. However, in many cases the mechanisms involved in the damage of the graft are unclear, as in the case of antibodies directed to HLA molecules that are not specific to the donor. Although it is well established the interrelation of humoral and cellular immune responses, little is known about the kinetics of anti-HLA antibodies post-transplantation and its relationship with the population of T and B regulatory cells, and their impact on graft outcome. Objective: To determine whether the kinetics of anti-HLA antibodies is related to the numbers of T and B regulatory cells, and their relation to the evolution of the graft. Methodology: This is a prospective observational study, in which individuals with kidney transplants will be monitored during the first 24 months of transplantation or until graft loss. The research subjects will be evaluated in the pre-transplant period and at various points after transplantation, clinically, and for the presence of class I and II anti-HLA antibodies directed to donor cells. The quantification of the subpopulations of T and B lymphocytic cells will be also evaluated. In selected cases, a functional analysis of these cells will be performed. We will seek to determine whether there is a relationship between these two immunological parameters and graft outcome.These data may contribute to increase the understanding of the relation between the components of humoral and cellular immune responses in renal transplantation, as well as for the determination of potential biomarkers of acute rejection or chronic rejection. (AU)