engleski

ANALYSIS OF THE KIR GENES IMPACT ON HEMATOPOIETIC STEM CELL TRANSPLANTATION OUTCOME ACCORDING TO THREE DIFFERENT PREDICTIVE MODELS FROM LITERATURE

One of the many factors influencing hematopoietic stem cell transplantation (HSCT) is the presence of donor- derived alloreactive NK cells that are formed mainly as the result of KIR-HLA ligand mismatching. Three models for predicting alloreactive NK cell formation exist: the ligand- ligand model, KIR receptor-ligand model and KIR haplotype model. The purpose of this study was to analyze the association of patient and donor KIR ligands, KIR genes and genotypes on HSCT outcome and to see which of the three models the best algorithm to predict HSCT outcomes is. The investigated group consisted of 56 patient-donor pairs that had undergone unrelated HSCT in University Hospital Centre Zagreb. Analysis according to the ligandligand model in the studied group resulted in only four mismatches as opposed to the KIR-ligand model where 31 patient-donor pairs were KIR-ligand mismatched, leading to the conclusion that determining KIR ligand mismatches only following patient-donor HLA typing, without KIR genotyping of donors, is not good prognostic algorithm. The inhibitory KIR-HLA ligand matches/mismatches determined with the KIR-ligand model did not show any beneficial effect of KIR ligand mismatches on any investigated HSCT endpoint. Assigning the AA or Bx KIR genotype to each patient and donor (patient/donor combinations: AA/AA, AA/Bx, Bx/AA and Bx/Bx) enabled its analysis according to the third model and, although no statistically significant difference was found, a trend towards better survival was observed in AA patients receiving a Bx graft. The conclusion is that any of existing models to predict alloreactive NK cell formation and their effect on HSCT outcomes can't give the answer alone and to clarify the KIR influence on HSCT outcome, different approaches in the analyses which encompasses all properties of KIR genes/receptors, KIR-ligands and NK cells together needs to be taken into consideration.

KIR genes, HSCT

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