HLA-DRB1 and HLA-DQB1 genes on susceptibility to and protection from allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.

ABSTRACT

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity pulmonary disease that affects both patients with cystic fibrosis (CF) and those with asthma. HLA-DRB1 alleles have previously been associated with ABPA-CF susceptibility; however, HLA-DQB1 allele associations have not been clearly established. The aim of the present study was to investigate HLA class II associations in patients with ABPA-CF and determine their roles in susceptibility or protection. Patients with ABPA-CF, patients with CF without ABPA, patients with asthma without ABPA (AST), and healthy controls were included in this study. DNA was extracted by automatic extractor. HLA-DRB1 and -DQB1 genotyping was performed by the Luminex PCR-SSOP method (One Lambda, Canoga Park, CA, USA). Allele specific PCR-SSP was also performed by high-resolution analysis (One Lambda). Statistical analysis was performed with SSPS and Arlequin software. Both HLA-DRB1*501 and -DRB1*1104 alleles occurred with greater frequency in patients with ABPA-CF than in those with AST and CF and control subjects, corroborating previously published data. On the other hand, analysis of haplotypes revealed that almost all patients with ABPA-CF lacking DRB1*1501 or DRB1*1104 carry either DRB1*04, DRB1*1101, or DRB1*0701 alleles. In the HLA-DQB1 region, the HLA-DQB1*0602 allele occurred more frequently in patients with ABPA-CF than in those with AST and CF and healthy controls, whereas HLA-DQB1*0201 occurred less frequently in patients with ABPA-CF. These data confirm that there is a correlation between HLA-DRB1*1501, -DRB1*1104, DRB1*1101, -DRB1*04 and -DRB1*0701 alleles and ABPA-CF susceptibility and suggest that HLA-DQB1*0201 is an ABPA-CF resistance allele.