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English summary: Immunogenetics of allogeneic stem cell transplantation and population genetics studies
HLA incompatibilities remain a main barrier to clinical transplantation. The developments of PCR-based tools to disclose HLA allelic polymorphism undetected by routine serological assays have allowed a better definition of HLA matching and a wider use of unrelated donors for allogeneic stem cell transplantation.
In collaboration with the Division of Hematology (HUG) and with the Swisstransplant working group for bone marrow transplantation (STABMT) we are analysing the impact of disparities at different HLA loci on clinical outcome. This analysis is also included in a collaborative study by the International Histocompatibility Working Group (IHWG) of the 15th International Histocompatibility and Immunogenetics Workshop.
The laboratory is involved in the characterization of new HLA variants in clinical samples analysed by the National Reference Laboratory for Histocompatibility (LNRH). Another part of the research project aims at building a database of extended HLA-A/B/C/DRB1 haplotypes (high resolution level) as an essential tool for a reliable predictive value of the probability to identify a compatible donor. Furthermore, using microsatellites polymorphisms we are exploring the potential role of non-HLA markers in the MHC on transplant outcome.
A particular focus is on microsatellites in the HLA class III region close to the TNF gene. In view of the growing importance of natural killer (NK)-mediated anti-leukemic alloreactivity the impact of KIR (killer immunoglubulin-like receptors)/KIR-ligand mismatches on clinical outcome are also studied. We plan to integrate HLA parameters with non-HLA immunogenetics so that individual assessments of genetic risk might be used for donor selection algorithms.
In a collaboration with Prof. A. Sanchez-Mazas (Department of Anthropology, Sciences Faculty) HLA diversity is analysed in populations from diverse ethnic groups worldwide, aiming at reconstituting human populations history. Future projects on the role of HLA markers in autoimmune diseases are planned with the Division of Rheumatology and with the Division of Ophtalmology (HUG)