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Humoral Immunity in Kidney Transplantation

Friday 24 July 2015

Humoral Immunity in Kidney Transplantation

Dr. H.G. Otten, dr. E. Kamburova, dr. B. Wisse

Project
The presence of complement fixing HLA antibodies against potential kidney donors prior to transplantation is considered a contraindication for transplantation. Although complement dependent crossmatching (CDC) is a widely used technique to detect these antibodies, this assay has a number of significant limits including the low resolution for antibody definition and low sensitivity. The national PROCARE consortium studies the impact of humoral allo- and auto-immunity in ~5000 kidney transplants and aims to modernize kidney allocation leading to improved kidney graft survival and less HLA-immunization (see web link below). The consequences of these antibodies binding to kidney endothelium are not fully understood including the efficacy of endothelial cells to self-protect against antibody-mediated damage. Databases generated in the project will provide novel insights into the exact specificities of antibodies including identification of those causing kidney graft rejection

Web link:
http://www.nierstichting.nl/werk/onderzoek/consortia-programma/consortium-2013

Question in research projects:
- The density of targets recognized by patient antibodies differs between endothelial cells from kidney donors. Does that matter with regard to rejection?
- Multiple cases are identified in which HLA antibodies against the donor kidney were present prior to transplantation according sensitive techniques, but the transplanted kidneys still perform well after many years. What are the mechanisms explaining resistance to rejection by HLA antibodies? Can we exploit that in other transplants?
- Does it matter which epitope is recognized by patient antibodies on patient HLA? In this project we will define detrimental versus clinically irrelevant HLA antibodies against donor kidneys.

Techniques
We use state-of-the-art techniques and database management, including molecular construction of vectors producing antigens allowing novel luminex-based autoantibody analysis, isolation and culture of donor kidney endothelial cells, building and extracting data from large relational databases.

Duration
6 or 9 months

Contact

Dr. H.G. Otten, h.g.otten@umcutrecht.nl 088-7557680
Dr. E.G. Kamburova, e.g.kamburova@umcutrecht.nl 088-7559024
Dr. B.W. Wisse, B.W.Wisse@umcutrecht.nl 088-7559024

Dr. Kristin Denzer, k.denzer@umcutrecht.nl 088-7564368

More information: : UMC Utrecht website Laboratory of Translational Immunology