title: KIR repertory in patients with hematopoietic diseases and healthy family members.
abstract: BACKGROUND
  Since the discovery of specific histocompatibility, literature has associated genes involved in the immune response, like the Human Leucocyte Antigen (HLA), with a better prognosis in transplantation. However, other non-HLA genes may also influence the immune process, such as the genes encoding the immunoglobulin-like receptors of natural killer cells (KIRs). The discovery that NK cell KIR receptors interact with conservative epitopes (C1, C2, Bw4) presented in HLA class I molecules that are genetically polymorphic, also observed in KIR genes, led to the investigation of the relevance of the KIR system to hematopoietic stem cell transplant. The cure of patients with leukemias and other hematological malignancies after bone marrow transplantation (BMT) has been attributed in part to the ability of the donor immune cells, present in the graft, to recognize and eliminate neoplastic cells of the patient. The cytotoxic activity of NK cells is mediated by the absence of HLA class I-specific ligands on the target cell surface to inhibitory KIR receptors (hypothesis of "missing-self").
  
  
  METHODS
  We analyzed, by PCR typing-SSOP technique, the presence or absence of 16 KIR genes and haplotypes of 39 patients with hematopoietic disorders and 136 healthy individuals from Paraná State. The comparisons made between the patient and control group were performed using χ2test or Fisher exact test (bilateralp-value), as appropriated. Significance level was considered whenp-value ≤ 0.05.
  
  
  RESULTS
  Framework genesKIR3DL3, KIR3DP1, KIR2DL4andKIR3DL2were positive in all samples. The comparison between KIR repertoire of patients and healthy individuals revealed significant differences (p< 0.05) in inhibitors genesKIR2DL2(p= 0.0005) andKIR2DL5(p= 0.0067) and activating genesKIR2DS1(p= 0.0013),KIR2DS2(p= 0.0038),KIR2DS3(p= 0.0153) that are more frequent in controls than in patients. TheKIR2DS3was significantly more frequent (p= 0.0031) in patients with acute myeloid leukemia (AML) when compared to patients with acute lymphoblastic leukemia (ALL). We observed a higher frequency of haplotype A (59 %) in the patients.
  
  
  CONCLUSIONS
  Our data suggests that susceptibility to leukemia can be influenced, at least, partly byKIR receptors.
authors.affiliation: Departamento de Genética, Laboratório de Imunogenética e Histocompatibilidade (LIGH), Universidade Federal do Paraná, R. Cel. Francisco H. dos Santos S/N, Centro Politécnico - Jardim das Américas, CEP 81.530.990, Curitiba, PR CP 19071 Brazil.
authors.forename: Daniele Kazue
authors.initials: DK
authors.lastname: Sugioka
authors.affiliation: Departamento de Genética, Laboratório de Imunogenética e Histocompatibilidade (LIGH), Universidade Federal do Paraná, R. Cel. Francisco H. dos Santos S/N, Centro Politécnico - Jardim das Américas, CEP 81.530.990, Curitiba, PR CP 19071 Brazil.
authors.forename: Carlos Eduardo Ibaldo
authors.initials: CE
authors.lastname: Gonçalves
authors.affiliation: Departamento de Genética, Laboratório de Imunogenética e Histocompatibilidade (LIGH), Universidade Federal do Paraná, R. Cel. Francisco H. dos Santos S/N, Centro Politécnico - Jardim das Américas, CEP 81.530.990, Curitiba, PR CP 19071 Brazil.
authors.forename: Maria da Graça
authors.identifier: 0000-0002-0588-6096
authors.initials: MD
authors.lastname: Bicalho
keywords: HLA; KIR; Leukemia