title: Human leucocyte antigen class II association in idiopathic bronchiectasis, a disease of chronic lung infection, implicates a role for adaptive immunity.
abstract: The aetiology of idiopathic bronchiectasis, a lung disease where chronic inflammation and bacterial infection leads to progressive lung damage, is unknown. A possible role for natural killer cells has been highlighted previously. However, a role for adaptive immunity is suggested by the presence of CD4 and CD8 T cells in diseased lung tissue. Evidence of a human leucocyte antigen (HLA) class II disease association would further implicate a role for adaptive immunity. To establish if there is any HLA association, we analysed HLA-A, HLA-B, HLA-DQA1, HLA-DQB1 and HLA-DRB1 alleles in patients with idiopathic bronchiectasis and controls. Genomic DNA from 92 adults with idiopathic bronchiectasis and 101 healthy controls was analysed by polymerase chain reaction with sequence-specific primers. We found an increase in the prevalence of HLA-DRB1*01 DQA1*01/DQB1*05 genes in idiopathic bronchiectasis; that is, the HLA-DR1, DQ5 haplotype (odds ratio 2.19, 95% confidence interval 1.15-4.16, P = 0.0152) compared with control subjects. The association with HLA-DR1, DQ5 implicates a role for CD4 T cells restricted by these molecules in susceptibility to the progressive lung damage seen in this disease. This may operate either through influencing susceptibility to specific pathogens or to self-reactivity and requires further investigation.
authors.affiliation: Lung Immunology Group, NHLI, Sir Alexander Fleming Building, South Kensington Campus, Faculty of Medicine, Imperial College, London, UK. r.boyton@imperial.ac.uk
authors.forename: R J
authors.initials: RJ
authors.lastname: Boyton
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Jones
authors.forename: C
authors.initials: C
authors.lastname: Reynolds
authors.forename: L
authors.initials: L
authors.lastname: Ozerovitch
authors.forename: A
authors.initials: A
authors.lastname: Chaudhry
authors.forename: R
authors.initials: R
authors.lastname: Wilson
authors.forename: M
authors.initials: M
authors.lastname: Rose
authors.forename: D M
authors.initials: DM
authors.lastname: Altmann
mesh_terms: D000328:Adult; D001987:Bronchiectasis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D015798:HLA-DR1 Antigen / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000150:complications*
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006683:HLA-DQ Antigens; C410042:HLA-DQ5 antigen; D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II