RATIONALE: Allergic bronchopulmonary aspergillosis occurs in 7-10% of cystic fibrosis (CF) and 1-2% of asthmatic patients. HLA-DR restriction and increased sensitivity to IL-4 stimulation have been proposed as risk factors in these populations. METHODS: We examined for the presence of IL-4 receptor alpha chain (IL-4Ra) single nucleotide polymorphisms (SNPs) in ABPA and whether these accounted for increased sensitivity to IL-4 stimulation. We then examined whether the combination of HLA-DR restriction and IL-4Ra SNPs were present as risk factor for the development of ABPA. RESULTS: IL-4Rα SNPs were observed in 93% of CF and in 86% of asthmatic ABPA patients. The predominant IL-4Ra SNP was an extracellular IL-4Ra SNP, ile75val, observed in 79% of CF and in 68% of asthmatic ABPA patients. The combination of HLA DR2/DR5 and ile75val SNP was found in 71% of CF and in 68% of ABPA patients. ABPA subjects also had significantly increased expression of CD23 molecules per B cell of IL-4 stimulated PBL cultures compared to controls. CONCLUSIONS: The combination of HLA-DR2/DR5 restriction associated with IL-4Ra SNP, principally ile75val, appears to be genetic risks for the development of ABPA.
Full conference title:
2006 American Academy of Allergy, Asthma, and Immunology Annual Meeting
- AAAAI 2006 (62nd)