The role of CD23 in IgE dependent signaling: implications from pharmacogenetics

The association of immunoglobulin E (IgE) with allergic diseases and asthma is well established. IgE binds to two receptors on various immune and inflammatory cells. The lower-affinity IgE Fc receptor, CD23, has multiple functions in enhancing the regulation of IgE production itself, and that of various pro-inflammatory activities and mediators. The data in this report are derived from an analysis of variation in the CD23 gene that leads to a coding exchange and to a single nucleotide polymorphism (SNP) associated with the substitution of an arginine residue for a tryptophan residue in the protein structure of CD23. This genetic variation is associated with three findings identified in this report. First, the tryptophan exchange is associated with greater expression of RNA for the interleukin (IL)-4 receptor alpha chain and greater expression of RNA for egr-1 transcription factor, both of which are proinflammatory gene products that influence allergy-related immune functions. Second, the exchange is associated with cell surface expression of IL-4R. Third, an analysis of potential arginine-to-tryptophan exchanges in the entire human genome has identified a number of interesting exchanges in immunologic genes of interest for their role in allergic responses. A discussion of these three findings is presented.