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

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 epsilon RI immunoprecipitates as a protein of similar to 40 kDa and contains an intact IgE-binding site. In human serum, 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.