Abstract:
INTRODUCTION: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. DISCUSSION: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.
journal_name
Respir Medjournal_title
Respiratory medicineauthors
McDonnell MJ,Anwar GA,Rutherford RM,De Soyza A,Worthy S,Corris PA,Lordan JL,Bourke S,Afolabi G,Ward C,Middleton P,Middleton Ddoi
10.1016/j.rmed.2014.05.017subject
Has Abstractpub_date
2014-08-01 00:00:00pages
1127-33issue
8eissn
0954-6111issn
1532-3064pii
S0954-6111(14)00223-6journal_volume
108pub_type
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