Humoral mechanisms of kidney transplant rejection: the anti-HLA and anti-endothelial cells antibodies role: a clinical and anatomo-pathological study

Abstract

Kidney transplantation is the best therapy for patients with chronic kidney disease. However, many grafts are still lost due to acute and chronic rejection. There is growing evidence that humoral as well cellular mechanisms are involved in rejection episodes. Since the appearance of new techniques for anti-HLA and non-HLA antibody detection and the introduction of C4d staining in graft biopsies plus the increase of the transplants performed in sensitized patients, new attention was given to humoral mechanisms in rejection episodes.Antibody mediated rejection is defined by the presence of morphologic evidence of acute or chronic tissue injury, serologic evidence of circulating antibodies to donor HLA or other anti-donor endothelial antigens and/or immunopathologic evidence for antibody activity (C4d) in the graft. There is consensus among researchers about the importance of anti-HLA antibodies in renal transplantation, and about the predictive factor of the presence of C4d in the graft. However, we observed that the majority of the studies performed, did not analyse the dinamics of these antibodies. Their time correlation with rejection episodes and with histological features in renal grafts were not well studied, neither in sensitized and not sensitized pacients, being difficult to define them as predictors of the rejection process. Analysing the available literature it is also inconclusive the physiopatogenic role of antibodies directed to anti-endothelial cells in rejection and graft loss. We propose a prospective and unicentric study to evaluate the presence and the dinamics of anti-HLA and anti-endothelial cells antibodies (AECA) before and after kidney transplantation. We propose also to compare these findings with the clinical evolution of the graft, with emphasis to rejection episodes that will be confirmed by immunopathological and immunological tests. (AU)