HLA allele and haplotype diversity in Croatia and its impact on donor selection in hematopoietic stem cell transplantation

Istraživanja raspodjele alela i haplotipova glavnog sustava tkivne snošljivosti (engl. Human Leukocyte Antigen, HLA) provode se u svrhu populacijskih istraživanja kao i u programu transplantacije krvotvornih matičnih stanica (TKMS) od HLA podudarnog nesrodnog davatelja. Ovim radom obuhvaćena je skupina od 10 000 zdravih nesrodnih dobrovoljnih davatelja iz Hrvatskog registra dobrovoljnih davatelja krvotvornih matičnih stanica (HRDDKMS) te skupina od 261 nesrodnog bolesnika u programu nesrodne TKMS. Svim ispitanicima analizirani su geni HLA-A, -B, -C i -DRB1 jednom od molekularnih metoda. Obradom podataka o učestalosti alela i haplotipova HLA dobivene su vrijedne informacije o raznolikosti alela HLA te čestim, rijetkim i vrlo rijetkim alelima i haplotipovima HLA u Hrvatskoj. Rezultati rada ističu važnost održavanja manjih i srednjih registara dobrovoljnih davatelja KMS čime se doprinosi prepoznavanju raznolikosti alela i haplotipova HLA. Također, ističu ulogu HLA kao ograničavajućeg čimbenika u pronalaženju fenotipski HLA podudarnog nesrodnog davatelja te služe unaprjeđenju postupka pronalaska najboljeg mogućeg davatelja za pojedinog bolesnika.Investigation of allele and haplotype distribution of genes pertaining to Human Leukocyte Antigen complex (HLA) is relevant for population studies but also in hematopoietic stem cell transplantation (HSCT) from HLA matched unrelated donor. This study encompassed 10 000 healthy unrelated volunteer donors from Croatian Bone Marrow Donor Registry (CBMDR) and 261 patients who underwent unrelated HSCT. All subjects were analyzed for HLA-A, -B, -C and -DRB1 genes by one of DNA analysis based methods. HLA allele and haplotype frequency analysis provided valuable information about HLA allelic polymorphism as well as data about common, rare and very rare HLA alleles and haplotypes in Croatia. Obtained results emphasize importance of maintaining small and medium size registries of HSC donors due to their contribution to HLA allele and haplotype diversity identification. Results also highlight the role of HLA as a limitation factor in identification of HLA phenotypically matched unrelated donor. Finally, data provided by this study will serve to improve the procedure of finding the best donor for a given patient