title: Lack of association between KIR and HLA-C type and susceptibility to idiopathic bronchiectasis.
abstract: BACKGROUND
  Idiopathic bronchiectasis is a poorly defined disease characterised by persistent inflammation, infection and progressive lung damage. Natural killer (NK) cells provide a major defense against infection, through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin-like receptors (KIR), and human leukocyte antigens (HLA) class I molecules. Homozygosity for HLA-C has been shown in a single study to confer increased genetic susceptibility to idiopathic bronchiectasis. We aimed to assess whether the KIR and HLA repertoire, alone or in combination, may influence the risk of developing idiopathic bronchiectasis, in an independent replication study.
  
  
  METHODS
  In this prospective, observational, case-control association study, 79 idiopathic bronchiectasis patients diagnosed following extensive aetiological investigation were compared with 98 anonymous, healthy, age, sex and ethnically-matched controls attending blood donor sessions in the same geographical location. DNA extraction was performed according to standardised techniques. Determination of presence or absence of KIR genes was performed by a sequence specific oligonucleotide probe method. Allele frequencies for the proposed KIR, HLA-B and HLA-C risk alleles both individually and in combinations were compared.
  
  
  RESULTS
  We found no significant differences in allele frequency between the idiopathic bronchiectasis and control samples, whether considering HLA-C group homozygosity alone or in combination with the KIR type.
  
  
  CONCLUSIONS
  Our results do not show an association between HLA-C and KIR and therefore do not confirm previous positive findings. This may be explained by the lower frequency of HLA-C1 group homozygosity in the control population of the previous study (27.2%), compared to 42.3% in our study, which is consistent with the genetic profiling of control groups across the UK. The previous positive association study may therefore have been driven by an anomalous control group. Further larger prospective multicentre replication studies are needed to determine if an association exists.
authors.affiliation: Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle, UK; Department of Respiratory Medicine, Galway University Hospitals, Galway, Ireland. Electronic address: melissajanefriel@gmail.com.
authors.forename: M J
authors.initials: MJ
authors.lastname: McDonnell
authors.affiliation: Department of Respiratory Medicine, Northumbria Healthcare Trust, Newcastle, UK.
authors.forename: G A
authors.initials: GA
authors.lastname: Anwar
authors.affiliation: Department of Respiratory Medicine, Galway University Hospitals, Galway, Ireland; Department of Respiratory Medicine, Northumbria Healthcare Trust, Newcastle, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Rutherford
authors.affiliation: Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
authors.forename: A
authors.initials: A
authors.lastname: De Soyza
authors.affiliation: Department of Radiology, Royal Victoria Infirmary, Newcastle, UK.
authors.forename: S
authors.initials: S
authors.lastname: Worthy
authors.affiliation: Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Corris
authors.affiliation: Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Lordan
authors.affiliation: Department of Respiratory Medicine, Northumbria Healthcare Trust, Newcastle, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bourke
authors.affiliation: Department of Respiratory Medicine, Northumbria Healthcare Trust, Newcastle, UK.
authors.forename: G
authors.initials: G
authors.lastname: Afolabi
authors.affiliation: Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
authors.forename: C
authors.initials: C
authors.lastname: Ward
authors.affiliation: Department of Academic Haematology, Medical School, Newcastle University, Newcastle, UK.
authors.forename: P
authors.initials: P
authors.lastname: Middleton
authors.affiliation: Department of Transplant Immunology, Royal Liverpool Hospital and School of Infection and Host Defence, Liverpool University, Liverpool, UK.
authors.forename: D
authors.initials: D
authors.lastname: Middleton
mesh_terms: D000368:Aged; D001987:Bronchiectasis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D011446:Prospective Studies; D054340:Receptors, KIR / Q000235:genetics*
chemical_list: D015235:HLA-B Antigens; D015236:HLA-C Antigens; D054340:Receptors, KIR
keywords: Bronchiectasis; HLA-C; Humans; Immunity; Killer cell immunoglobulin-like receptor