HLA-C and killer cell immunoglobulin-like receptor genes in idiopathic bronchiectasis.
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.
Boyton
Rosemary J
RJ
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
Smith
John
J
Ward
Rosemary
R
Jones
Meinir
M
Ozerovitch
Lorraine
L
Wilson
Robert
R
Rose
Marlene
M
Trowsdale
John
J
Altmann
Daniel M
DM
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
D015236:HLA-C Antigens; D011971:Receptors, Immunologic; D054340:Receptors, KIR