Abstract
Background:
Allergic bronchopulmonary aspergillosis (ABPA) is a bronchial allergic inflammatory reaction to Aspergillus fumigatus that occurs in a minority of susceptible asthmatic and cystic fibrosis (CF) patients. Previous studies identified that HLA-DR2/DR5 was associated with susceptibility to develop ABPA; however, HLA-DR2/DR5 occurs frequently in non-ABPA patients as well.
Objective:
We hypothesize that in addition to HLA-DR restriction, other genetic risk factors predispose asthmatic and CF patients to develop ABPA. Methods: HLA-DR and interleukin-4 (IL-4) receptor α-chain (IL-4RA), IL-13, and IL-10 -1082 polymorphisms were examined in 41 asthmatic and CF patients with ABPA and in 84 asthmatic and CF non-ABPA patients.
Results:
HLA-DR2 and/or DR5 were identified in 70.7% of ABPA patients and in 35.7% of non-ABPA patients. IL-4RA single-nucleotide polymorphisms (SNPs) were present in 95% of ABPA patients, with the ile75val SNP in 80.5% of ABPA patients. Both HLA-DR2/DR5 and IL-4RA SNPs individually were associated with increased risk for the development of ABPA; however, the combination of HLA-DR2/DR5 and ile75val predicted the greatest risk with an odds ratio (OR) of 6.6. There was a trend for increased frequency of the IL-10 -1082 GG genotype in ABPA patients, and the combination of HLA-DR2/DR5, ile75val and IL-10 -1082 G genotype was associated with increased risk in the development of ABPA, OR 8.0. The IL-13 arg110gln SNP was not increased in ABPA patients.
Conclusions:
Genetic risks for the development of ABPA include HLA-DR2/DR5 and IL-4RA ile75val and IL-10 -1082G polymorphisms.