title: Interactions between killer immunoglobulin-like receptors and their human leucocyte antigen Class I ligands influence the outcome of unrelated haematopoietic stem cell transplantation for thalassaemia: a novel predictive algorithm.
abstract: In a study conducted on 114 patients undergoing unrelated donor haematopoietic stem cell transplantation (HSCT) for thalassaemia, we observed that the lack of activating killer immunoglobulin-like receptors (KIRs) on donor natural killer (NK) cells significantly increased the risk of graft-versus-host disease (GvHD) [hazard risk (HR) 4.2, 95% confidence interval (CI) 1.7-10.1, P = 0.002] and transplantation-related mortality (HR 4.7, 95% CI 1.6-14.2, P = 0.01). The risk of GvHD furthermore increased when recipients heterozygous for HLA-C KIR ligand groups (C1/C2) were transplanted from donors completely lacking activating KIRs (HR 6.1, 95% CI 1.9-19.2, P = 0.002). We also found that the risk of rejection was highest when the recipient was homozygous for the C2 HLA-KIR ligand group and the donor carried two or more activating KIRs (HR 6.8, 95% CI 1.9-24.4, P = 0.005). By interpolating the number of donor activating KIRs with recipient HLA-C KIR ligands, we created an algorithm capable of stratifying patients according to the immunogenetic risk of complications following unrelated HSCT. In clinical practice, this predictive tool could serve as an important supplement to clinical judgement and decision-making.
authors.affiliation: Centro Regionale Trapianti, Ospedale R. Binaghi - ASL 8, Cagliari, Italy. litter@tiscali.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Littera
authors.forename: Nicola
authors.initials: N
authors.lastname: Orrù
authors.forename: Giovanni
authors.initials: G
authors.lastname: Caocci
authors.forename: Marco
authors.initials: M
authors.lastname: Sanna
authors.forename: Marina
authors.initials: M
authors.lastname: Mulargia
authors.forename: Eugenia
authors.initials: E
authors.lastname: Piras
authors.forename: Adriana
authors.initials: A
authors.lastname: Vacca
authors.forename: Claudio
authors.initials: C
authors.lastname: Giardini
authors.forename: Maria G
authors.initials: MG
authors.lastname: Orofino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Visani
authors.forename: Alice
authors.initials: A
authors.lastname: Bertaina
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giorgiani
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Carlo
authors.initials: C
authors.lastname: Carcassi
authors.forename: Giorgio
authors.initials: G
authors.lastname: La Nasa
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D060005:Genotyping Techniques; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008024:Ligands; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011379:Prognosis; D011485:Protein Binding / Q000276:immunology; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology; D012189:Retrospective Studies; D013789:Thalassemia / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D054340:Receptors, KIR