Published ahead of print on October 27, 2005, doi:10.1164/rccm.200501-124OC Am. J. Respir. Crit. Care Med., Volume 173, Number 3, February 2006, 327-333 A more recent version of this article appeared on February 1, 2006
Submitted on January 26, 2005 HLA-C and Killer Cell Immunoglobulin-Like Receptor (KIR) Genes in Idiopathic BronchiectasisRosemary J Boyton1*,1 Department of Biological Sciences, NHLI, Lung Immunology Group, Imperial College, London, United Kingdom; Department of Respiratory Medicine, Host Defense Unit, Royal Brompton and Harefield NHS Trust, London, United Kingdom, 2 Heart Science Centre, Imperial College, Harefield Hospital, Harefield, United Kingdom, 3 Department of Pathology, Immunology Division, University of Cambridge, Cambridge, United Kingdom, 4 Department of Occupational and Environmental Medicine, NHLI, Imperial College, London, United Kingdom, 5 Department of Respiratory Medicine, Host Defense Unit, Royal Brompton and Harefield NHS Trust, London, United Kingdom, 6 Department of Infectious Diseases, Human Disease Immunogenetics Group, Imperial College, London, United Kingdom * To whom correspondence should be addressed. E-mail: r.boyton{at}imperial.ac.uk.
Rationale. In idiopathic bronchiectasis, lung inflammation and chronic bacterial infection leads 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. Since the HLA-C locus and KIRs are of key importance for NK cell recognition, we analyzed HLA-C/KIR combinations by genotyping of patients with idiopathic bronchiectasis. Methods. Genomic DNA from 96 individuals with idiopathic bronchiectasis and 101 controls was analyzed by PCR with sequence specific primers (PCR-SSP). High resolution HLA-C genotyping was carried out in addition to KIR analysis. Results. HLA-Cw*03 alleles and, in particular, HLA-C group 1 homozygosity, is associated with the presence of bronchiectasis. Analysis of the relationship between HLA-C and KIR genes suggests a shift to activatory NK cell function. Conclusion. 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/KIR genes, argue for a role of NK cells in the progressive lung damage seen in this disease. This will require further investigation using functional studies. Key words: Humans, Immunity, HLA-C, KIR (killer cell immunoglobulin-like receptor), bronchiectasis
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