ABSTRACT Allergic bronchopulmonary aspergillosis (ABPA) is a Th2 allergic hypersensitivity lung disease due to bronchial colonization of Aspergillus fumigatus that affects 1-2% of asthmatic and 7-9% of cystic fibrosis (CF) patients. We hypothesize that genetic risk factors predispose these patients to develop ABPA. We previously reported HLA-DR2 and DR5 restriction as a risk factor for the development of ABPA. We further propose that HLA-DR restriction is necessary but not sufficient for the development of ABPA. Recently, we reported that IL-4Rα single nucleotide polymorphisms (SNP) and in particular the ile75val SNP in the IL-4 binding region is another risk factor and is associated with increased sensitivity to IL-4 stimulation. In preliminary studies, we have observed increased frequency of the IL-13 SNP, arg110gln, frequently in combination with the ile75val IL-4Rα SNP. We propose that increased sensitivity of IL-4 and IL-13 mediated activities secondary to polymorphisms in conjunction with HLA-DR2/DR5 restriction to Aspergillus antigens in ABPA patients results in increased B-cell activity, monocyte/dendritic cell phenotype that skews Aspergillus-specific Th2 cells.
Buy this Article
|