Rationale Single nucleotide polymorphisms (SNPs) in the coding region of the IL-4Rα gene resulting in amino acid substitutions have been associated with atopic phenotypes. We report on the presence of 4 SNPs, E375A, C406R, S478P, and Q551R, (numbering including the 25-amino-acid signal peptide), of the IL-4Rα intracellular domain associated with increased IL-4 stimulated CD23 expression in a CF patient with ABPA. Methods DNA was extracted from cultures of B-cell lines of our patient with a diagnosis of CF and ABPA and from controls (non-ABPA with CF and non-ABPA without CF). Subjects were genotyped for the region of the IL-4Rα containing the desired 4 polymorphisms. IL-4 stimulated PBLs from our patient and controls were also examined for the expression of CD23, the low affinity IgE receptor, on B-cells. Results In our patient we found that the portion of the gene coding for the intracellular domain of the IL-4Rα contained all 4 of the SNPs for which we searched. This is in comparison to control subjects in whom no SNPs were found. Our patient also had significantly increased expression of CD23 molecules/B-cell of IL-4 stimulated PBL cultures compared to controls but similar to other patients with ABPA. Conclusions Thus multiple polymorphisms in the IL-4Rα gene may not only confer susceptibility to atopic diseases such as asthma, but also play a role in the risk of developing ABPA in certain patients with cystic fibrosis.
Full conference title:
2004 American Academy of Allergy, Asthma, and Immunology Annual Meeting
- AAAAI 2004 (60th)