title: HLA-C and killer cell immunoglobulin-like receptor genes in idiopathic bronchiectasis.
abstract: BACKGROUND
  In idiopathic bronchiectasis, lung inflammation and chronic bacterial infection lead to progressive lung damage. A possible role for natural killer (NK) cells is suggested by the observation that familial bronchiectasis occurs in a rare group of individuals with impaired HLA class I expression and consequent NK cell dysfunction.
  
  
  OBJECTIVE
  Because the HLA-C locus and killer cell immunoglobulin-like receptors (KIRs) are of key importance for NK cell recognition, we analyzed HLA-C/KIR combinations by genotyping patients with idiopathic bronchiectasis.
  
  
  METHODS
  Genomic DNA from 96 individuals with idiopathic bronchiectasis and 101 control subjects was analyzed by polymerase chain reaction with sequence-specific primers. High-resolution HLA-C genotyping was performed in addition to KIR analysis.
  
  
  RESULTS
  HLA-Cw*03 alleles and, in particular, HLA-C group 1 homozygosity are associated with the presence of bronchiectasis. Analysis of the relationship between HLA-C and KIR genes suggests a shift to activatory NK cell function.
  
  
  CONCLUSIONS
  This is the first demonstration of genetic susceptibility in idiopathic bronchiectasis. The association with HLA-C group 1 homozygosity, and the interplay between HLA-C and KIR genes, argue for a role for NK cells in the progressive lung damage seen in this disease. This will require further investigation using functional studies.
authors.affiliation: Lung Immunology Group, Department of Biological Sciences/National Heart and Lung Institute, Sir Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK. r.boyton@imperial.ac.uk
authors.forename: Rosemary J
authors.initials: RJ
authors.lastname: Boyton
authors.forename: John
authors.initials: J
authors.lastname: Smith
authors.forename: Rosemary
authors.initials: R
authors.lastname: Ward
authors.forename: Meinir
authors.initials: M
authors.lastname: Jones
authors.forename: Lorraine
authors.initials: L
authors.lastname: Ozerovitch
authors.forename: Robert
authors.initials: R
authors.lastname: Wilson
authors.forename: Marlene
authors.initials: M
authors.lastname: Rose
authors.forename: John
authors.initials: J
authors.lastname: Trowsdale
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Altmann
mesh_terms: D001987:Bronchiectasis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000235:genetics*; D054340:Receptors, KIR
chemical_list: D015236:HLA-C Antigens; D011971:Receptors, Immunologic; D054340:Receptors, KIR