title: Donor Killer Immunoglobulin-Like Receptor Haplotype B/x Induces Severe Acute Graft-versus-Host Disease in the Presence of Human Leukocyte Antigen Mismatch in T Cell-Replete Hematopoietic Cell Transplantation.
abstract: Natural killer cells have been identified as a mediator of alloimmune reactions in allogeneic hematopoietic stem cell transplantation (HSCT). Killer immunoglobulin-like receptors (KIRs) are an important determinant of natural killer cell function. The relationship between KIR genotypes/haplotypes and clinical outcomes of allogeneic HSCT is complex and inconsistent among several reports. We assessed the clinical impact of KIR haplotype on T cell-replete allogeneic HSCTs performed in a single Japanese center for hematological malignancies (n = 106). A comparison of 2 groups, donor haplotypes A/A and B/x, revealed no significant differences in overall survival, relapse, and nonrelapse mortality. However, grade III to IV acute graft-versus-host disease (GVHD) occurred significantly more frequently in the KIR haplotype B/x group (A/A versus B/x: 4.9% versus 20.0%; P = .02). This was even more evident when HLA mismatch was present. The highest incidences of grade II to IV and grade III to IV acute GVHD were observed in patients who received allografts from HLA-mismatched donors with KIR haplotype B/x. These data highlight the importance of KIR genotyping in donor matching, especially when HLA mismatch allogeneic grafting is planned.
authors.affiliation: Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Hosokai
authors.affiliation: Division of Stem Cell Transplantation, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Masuko
authors.affiliation: Division of Stem Cell Transplantation, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Shibasaki
authors.affiliation: Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Saitoh
authors.affiliation: Division of Stem Cell Transplantation, Niigata University Medical and Dental Hospital, Niigata, Japan. Electronic address: tatsuof@nagaoka.jrc.or.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. Electronic address: chihaya@med.niigata-u.ac.jp.
authors.forename: Chihaya
authors.initials: C
authors.lastname: Imai
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006648:Histocompatibility; D006801:Humans; D007564:Japan; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics / Q000276:immunology*; D012189:Retrospective Studies; D014019:Tissue Donors; D000075442:Transplantation, Haploidentical / Q000009:adverse effects* / Q000379:methods; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D054340:Receptors, KIR
keywords: Acute graft-versus-host disease; Allogeneic hematopoietic cell transplantation; Killer immunoglobulin-like receptor haplotype