title: Role of killer immunoglobulin-like receptor-ligand interactions in human leukocyte antigen-matched sibling hematopoietic stem cell transplantation.
abstract: BACKGROUND
  Killer immunoglobulin-like receptor (KIR)-ligand mismatches lead to natural killer cell alloreactivity after hematopoietic stem cell transplantation (HSCT). However, their clinical impact on HSCT outcomes is controversial due to complexity of KIR haplotypes, genotypes, and phenotypes as well as their diversity among patient populations. The present study investigated the role of KIR-ligand interactions in human leukocyte antigen (HLA)-matched sibling transplants.
  
  
  METHODS
  The recipient cohort, which included patients diagnosed with aplastic anemia, acute leukemia, and myelodysplastic syndrome, received granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells. HLA typing was performed using polymerase chain reaction - sequence specific oligo probes (PCR-SSO). The KIR genotype of the donors and the ligands C1 (Asparagine 80), C2 (Lysine 80), and Bw4 recipient typings were performed using polymerase chain reaction - sequence specific primers (PCR-SSP). We assessed acute and chronic graft-versus-host disease (GVHD), relapse, and overall survival.
  
  
  RESULTS
  While 84.5% of donors carried a Bx KIR, 15.5% carried the AA haplotype. The effect of a recipient's lack of ligands among 88.5% of cases was associated with 39% of subjects developing GvHD. Lack of C1 may lead to manifestations of acute GvHD and lack of C2 to manifestation of chronic GvHD. The presence of both C1 and C2 seemed to be protective against both forms of GvHD. The role of two Bw4 alleles, threonine (T) or isoleucine (I) at position 80, was evaluated. 73% of recipients who carried Bw4 80(I) versus 27% with the Bw4 80(T) allele. The presence of Bw4-80(T) allele appeared to reduce the risk of GvHD, indicating its stronger inhibitory effect than its 80(I) counterpart.
  
  
  CONCLUSIONS
  KIR-ligand interactions influenced HSCT outcomes.
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India. umakanga@hotmail.com
authors.forename: U
authors.initials: U
authors.lastname: Kanga
authors.forename: M
authors.initials: M
authors.lastname: Mourya
authors.forename: T
authors.initials: T
authors.lastname: Seth
authors.forename: J
authors.initials: J
authors.lastname: George
authors.forename: P
authors.initials: P
authors.lastname: Sood
authors.forename: R
authors.initials: R
authors.lastname: Sharma
authors.forename: A
authors.initials: A
authors.lastname: Saxena
authors.forename: N K
authors.initials: NK
authors.lastname: Mehra
mesh_terms: D000208:Acute Disease; D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D002908:Chronic Disease; D005260:Female; D005787:Gene Frequency; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006648:Histocompatibility; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007194:India; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D008024:Ligands; D019520:Living Donors; D008297:Male; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D054340:Receptors, KIR / Q000235:genetics / Q000276:immunology*; D012008:Recurrence; D035781:Siblings; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D008024:Ligands; D054340:Receptors, KIR