title: Killer immunoglobulin-like receptor genotype in immune-mediated bone marrow failure syndromes.
abstract: OBJECTIVE
  Recent reports have shown that killer immunoglobulin-like receptors (KIR) and KIR ligand (KIR-L) genotype play a role in the pathophysiology of autoimmune disorders. Certain KIR/KIR-L combinations might convey a predisposition to immune-mediated bone marrow failure. Examining the genotypic makeup of human leukocyte antigen (HLA) class I (KIR-L) and KIR in patients with hematologic disorders could offer clues to immunogenetic risk factors for these diseases. The objective of this study is to establish the frequency of specific KIR genes and KIR-L alleles in aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia (MDS), and large granular lymphocyte leukemia (LGL), as compared with healthy control patients.
  
  
  METHODS
  KIR genotyping was performed on DNA from 113 patients with AA, PNH, MDS, and LGL using sequence specific primer amplification. Results of genotypic KIR analysis were examined with HLA typing. Comparisons in frequency of KIR-L groups, KIR genotype profiles, and KIR/KIR-L mismatch were performed to determine whether specific KIR genes and KIR-L are overrepresented in bone marrow failure states.
  
  
  RESULTS
  No difference in frequency of KIR-L groups was found relative to the healthy controls. AA and PNH showed decreased frequency of KIR-2DS1 and KIR-2DS5 genes: KIR-2DS1 35% vs 21% (p = 0.15) for AA and 19% for PNH (p = 0.13); KIR-2DS5 31% vs 14% (p = 0.08) for AA and 12% (p = 0.06) for PNH. These differences were even greater when compared to a larger group of control individuals from a study with similar genetic background.
  
  
  CONCLUSIONS
  The reduced frequency of these KIR in AA and PNH may indicate an immunogenetic relationship between these diseases.
authors.affiliation: Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland, OH 44195, USA.
authors.forename: Evan C
authors.initials: EC
authors.lastname: Howe
authors.forename: Marcin
authors.initials: M
authors.lastname: Wlodarski
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Ball
authors.forename: Lisa
authors.initials: L
authors.lastname: Rybicki
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
mesh_terms: D000741:Anemia, Aplastic / Q000235:genetics / Q000276:immunology; D001855:Bone Marrow Diseases / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D005787:Gene Frequency; D005838:Genotype; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007109:Immunity; D007945:Leukemia, Lymphoid / Q000235:genetics / Q000276:immunology; D008024:Ligands; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics*; D054340:Receptors, KIR; D013577:Syndrome
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR