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Kidney Disease Marta Crespo and Clara Barrios

Tornar

Immunological monitoring of renal transplants and chronic graft dysfunction

Endorsed by the ISCIII with three consecutive projects (PI Dr. Julio Pascual) for the periods 2011-2013, 2014-2016 and 2016-2019, the latter involving Dr. Marta Crespo as co-PI. A fourth project in this area has been awarded funding for the period 2021-23, led by Dr. Crespo.

The research focuses on monitoring the humoral and cellular immune response to renal transplant and its clinical correlation. The aim is to contribute to improving transplant access for patients with unusual immunological risk and also to clarify the process that triggers chronic humoral rejection.

We systematically evaluate the humoral, cellular and histological response in transplant recipients with donor-specific antibodies (DSA) in order to characterise chronic humoral rejection, identify biomarkers and stratify different therapeutic strategies according to each patient's profile.

We look at DSA production, modification over time, complement binding capacity and isotype distribution, renal graft biopsies of patients with DSA using conventional studies, tissue lymphocyte subpopulations, chimerism and electron microscopy and the distribution of these subpopulations, and the functionality of memory B cells and NK cells.

In addition, the group explores mechanisms involved in damage such as complement activation, innate immunity and activation of intracellular pathways. These projects highlight the fact that some kidney transplant patients have humoral rejection without DSA, which is an "orphan" entity of interest to the group.

The impact of changes in immunosuppression and the efficacy of various therapeutic approaches are also assessed in terms of their results.

The most recent project funded incorporates the characterisation of individuals who are candidates for renal transplantation using new data analysis tools and the study of antibody-producing memory B cells in our laboratory.

In addition to the aforementioned research projects, the group has benefited from two grants from La Marató de TV3:

• 2013-2015: "Study of NK cell contribution to chronic kidney transplant rejection in response to specific anti-HLA antibodies, genetic incompatibility and CMV infection", 400m€, 3 centres coordinated by Dr. Crespo.
• 2019-2021: for the study "Adaptive NK cell-mediated response to cytomegalovirus in the context of immunosuppression: clinical implications in renal transplantation", a consequence of the work of the previous project and the combination of the research efforts of nephrologists and immunologists from IMIM-UPF led by Dr. M López-Botet.