Genetic variations in the CεmX domain of human membrane-bound IgE

The ε chain of membrane-bound IgE (mIgE) is expressed predominantly as a “long” isoform, containing an extra segment of 52 amino acid (a.a.) residues, referred to as CεmX, between the CH4 domain and the C-terminal membrane-anchoring transmembrane peptide. CεmX results from an alternative splicing of the ε RNA transcript at 156-bp upstream of the splicing acceptor site used by the “short” isoform. Here, based on an analysis of the CεmX genomic DNA sequences of 320 subjects residing in Taiwan, we report that single-nucleotide polymorphisms have been found at two positions, namely, G/T at #46 and A/G at #93 (along the 156 bp of CεmX), with the former creating an amino acid change from Val to Leu at #16 (along the 52 a.a. of CεmX) and the latter resulting in no change (Gly). Among the 640 CεmX sequences identified, the previously known 46G93A allelic form appeared 293 times, the newly discovered 46T93A allelic form (GeneBank accession no. GU208817) 26 times, and the 46G93G allelic form (GU208818) 321 times. No 46T93G allelic form was found. Serum IgE measurements showed that the polymorphisms did not correlate with the levels of serum IgE. The anti-CεmX monoclonal antibody, 4B12, could bind equally well to mIgE.FcL(16V) and mIgE.FcL(16L). While genetic variation of CεmX of broader populations should also be investigated, these newly discovered genetic variants of CεmX in the Taiwanese population do not seem to affect the feasibility of using an anti-CεmX mAb, such as 4B12, to target mIgE-expressing B cells.