title: KIR/HLA-I mismatching and risk of relapse in paediatric patients undergoing non-haploidentical allogeneic haematopoietic stem cell transplantation.
abstract: In HSCT setting, KIR-driven alloreactivity might be better predicted if the donor KIR genotype is considered in addition to the recipient HLA genotype. The prediction of NK cell alloreactivity relies on the missing ligand in the recipient, a scenario that can be found in HLA-identical and non-identical allotransplants. The aim of this study was to investigate at genetic level the prognostic impact of recipient HLA-I lacking for donor KIR on allotransplanted patients outcome. We analysed donors KIR genotype and HLA genotype of 60 paediatric patients who received related (n=15) or unrelated (n=45) transplantation. When patients were grouped based on the KIR gene type involved in the KIR/HLA-I mismatch, we did not observe any relapse in the group of patients characterized by mismatches involving only inhibitory KIR. On the contrary, all relapses were observed in patients showing at least one activating gene involved in the mismatch (p<0.05). Although the biological mechanism accounting for this putative genetic rule is still to be clarified, we suggest that a careful survey of KIR/HLA-I mismatching should be taken into account in the selection of donor in related and unrelated HSCT.
authors.affiliation: Department of Clinical and Experimental Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine Venetian Institute for Molecular Medicine (VIMM), Centro di Eccellenza per la Ricerca Biomedica, Padua, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Scquizzato
authors.forename: Renato
authors.initials: R
authors.lastname: Zambello
authors.forename: Antonella
authors.initials: A
authors.lastname: Teramo
authors.forename: Ilenia
authors.initials: I
authors.lastname: Baesso
authors.forename: Stefania
authors.initials: S
authors.lastname: Varotto
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Albergoni
authors.forename: Elisa
authors.initials: E
authors.lastname: Boscaro
authors.forename: Simone
authors.initials: S
authors.lastname: Cesaro
authors.forename: Marta
authors.initials: M
authors.lastname: Pillon
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Calore
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Gazzola
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Semenzato
authors.forename: Chiara
authors.initials: C
authors.lastname: Messina
authors.forename: Livio
authors.initials: L
authors.lastname: Trentin
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D053843:DNA Mismatch Repair / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics; D015788:HLA-A1 Antigen / Q000032:analysis / Q000235:genetics*; D006238:Haploidy; D019337:Hematologic Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006648:Histocompatibility / Q000235:genetics; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D054340:Receptors, KIR / Q000032:analysis / Q000235:genetics*; D012008:Recurrence; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D015788:HLA-A1 Antigen; D054340:Receptors, KIR