title: The impact of HLA-C matching depends on the C1/C2 KIR ligand status in unrelated hematopoietic stem cell transplantation.
abstract: It was previously shown that chronic myeloid leukemia (CML) patients transplanted with peripheral blood progenitor cells (PBPC) from HLA-C allele-matched donors had better clinical outcome when lacking the HLA-C-encoded KIR epitope C2. We investigated whether this holds true in other diseases and in HLA-C allele-mismatched patients. Twenty-four myelodysplastic syndrome (MDS), 39 acute myeloid leukemia (AML)/CML, and 34 acute lymphoblastic leukemia/non-Hodgkin lymphoma patients received unrelated unmanipulated PBPC. HLA matching was analyzed retrospectively (including DNA-based direct sequencing of HLA-C). Only in AML/CML, the C2 ligand was associated with impaired overall survival (OS, p < 0.05). We next calculated the impact of donor/recipient HLA-C allele matching within the C1 and C2 groups. Surprisingly, AML/CML and MDS patients with C2 ligands profited from HLA-C allele mismatching (OS, p < 0.01), whereas in the C1 group, allele matching was beneficial (p < 0.05). HLA-C allele mismatching in the C2 KIR ligand group was associated with lower TRM (OR 0.48, p < 0.009) and lower relapse rate (OR 2.7 p < 0.1) when compared to allele-matched C2 patients. Thus, patients could be assigned to a low- and a high-risk group according to their C1/C2 ligand status and the HLA-C allele matching degree. These data suggest that four-digit allele matching of HLA-C has differential effects dependent on the presence of C1 and C2 KIR epitopes in the patient.
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University, Moorenstrasse 5, 40225, Düsseldorf, Germany. fischer@itz.uni-duesseldorf.de
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Fischer
authors.forename: Guido
authors.initials: G
authors.lastname: Kobbe
authors.forename: Jürgen
authors.initials: J
authors.lastname: Enczmann
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Markus
authors.initials: M
authors.lastname: Uhrberg
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000601:surgery; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000401:mortality / Q000601:surgery; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000401:mortality / Q000601:surgery; D054340:Receptors, KIR / Q000276:immunology*; D012189:Retrospective Studies; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D015236:HLA-C Antigens; D054340:Receptors, KIR