A Soluble Form of the High Affinity IgE Receptor, Fc-Epsilon-RI, Circulates in Human Serum

Abstract

Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFc\(\epsilon\)RI), the high affinity receptor for IgE. sFc (sFc\(\epsilon\)RI immunoprecipitates as a protein of ~40 kDa and contains an intact IgE-binding site. In human serum, sFc (sFc\(\epsilon\)RI) is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFc\(\epsilon\)RI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFc\( \epsilon \)RI. After IgE-antigen-mediated crosslinking of surface Fc\(\epsilon\)RI, we detect sFc\(\epsilon\)RI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFc\(\epsilon\)RI can block binding of IgE to Fc\(\epsilon\)RI expressed at the cell surface. In summary, we here describe the alpha-chain of Fc\(\epsilon\)RI as a circulating soluble IgE receptor isoform in human serum.