IMIM - Institut Hospital del Mar d'Investigacions Mèdiques

Kidney Disease Julio Pascual

Tornar

Kidney Transplantation and Immune Response

Monitoring of humoral and cell immune response in kidney transplantation and its clinical correlation.

This study can contribute to shedding light on the long process which leads to chronic humoral rejection. The development of drugs such as cyclopsporin or tacrolimus has enabled the massive decrease in acute kidney rejection, but the slow loss of function of the transplanted kidney continues to be detected along with the frequent onset of tumours and cardiovascular events. These facts have given rise to immunosuppression regimens without these drugs. It is important to identify the immunity causes of chronic dysfunction beyond pharmacological nephrotoxicity. If it is confirmed that patient transplants which develop anti-HLA antibodies fail more often and more is known about the chronological sequence for the appearance of antibodies and alloreactive cells, complement activation, histologic damage and clinical disease, it will be possible to systematise post kidney transplantation immunity monitoring. This will enable the development of immunosuppressive strategies aimed at eliminating the antibodies and cells responsible. On the other hand, those antibody-free recipients could benefit from reduced immunosuppression.

We will systematically evaluate late humoral response following kidney transplantation (post KT) by monitoring donor-specific anti-HLA antibodies, activating lymphocytes B and their different populations, as well as T cell populations and their ELISPOT reactivity, with the aim of determining various immune response patterns and correlating them with events and clinical evolution. The appearance of post-KT de novo anti-HLA antibodies, their specificity, and their modification in time will be correlated with the functioning of the transplanted organ, the treatment prescribed and its ability to activate peripheral blood B cells. Other objectives will include correlating the presence or modification of post-KT anti-HLA antibodies with mRNA expression levels, in peripheral blood mononuclear cells, of the B cell growth factor (BAFF) and of the Tribbles-1 potential biomarker of chronic kidney damage in transplanted patients, as well as the presence of regulating lymphocyte populations and donor-specific reactivity with clinical events. The research team aims to confirm that monitoring antibodies and various B and T lymphocyte activation parameters and their subpopulations are very significantly correlated with clinical events. This correlation will enable the future design of treatment intervention trials, in which it could be specifically modulated enabling us to individualise the need for pharmacological immunosuppression in each transplant recipient.

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