title: 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*5:01 and -DRB1*11:04 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*15:01 or DRB1*11:04 carry either DRB1*04, DRB1*11:01, or DRB1*07:01 alleles. In the HLA-DQB1 region, the HLA-DQB1*06:02 allele occurred more frequently in patients with ABPA-CF than in those with AST and CF and healthy controls, whereas HLA-DQB1*02:01 occurred less frequently in patients with ABPA-CF. These data confirm that there is a correlation between HLA-DRB1*15:01, -DRB1*11:04, DRB1*11:01, -DRB1*04 and -DRB1*07:01 alleles and ABPA-CF susceptibility and suggest that HLA-DQB1*02:01 is an ABPA-CF resistance allele.
authors.affiliation: Immunology Service, University Hospital Virgen Arrixaca, Madrid-Cartagena Rd, 30120, El Palmar, Murcia, Spain. manuel.muro@carm.es
authors.forename: Manuel
authors.initials: M
authors.lastname: Muro
authors.forename: Pedro
authors.initials: P
authors.lastname: Mondejar-López
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Moya-Quiles
authors.forename: Gema
authors.initials: G
authors.lastname: Salgado
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Pastor-Vivero
authors.forename: Ruth
authors.initials: R
authors.lastname: Lopez-Hernandez
authors.forename: Francisco
authors.initials: F
authors.lastname: Boix
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Campillo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Minguela
authors.forename: Ana
authors.initials: A
authors.lastname: Garcia-Alonso
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Solís
authors.forename: María Rocío
authors.initials: MR
authors.lastname: Álvarez-López
mesh_terms: D001229:Aspergillosis, Allergic Bronchopulmonary / Q000235:genetics*; D003550:Cystic Fibrosis / Q000150:complications; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D016133:Polymerase Chain Reaction
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains