Soluble FcεRI is increased in advanced-mastocytosis and acts as negative-regulator of mast cell-expansion and activation

The soluble alpha chain of the FcεRI (sFcɛRI) is released during receptor cross-linking on mast cells and serves as acceptor-site for circulating IgE. Recent data suggest that sFcɛRI counteracts mast cell activation in allergic patients. We measured the levels of sFcɛRI and its impact in cutaneous mastocytosis (CM) and systemic mastocytosis (SM). sFcɛRI levels were quantified by ELISA in 114 patients with mastocytosis, including CM (n=12), indolent SM (ISM, n=67), smoldering SM (SSM, n=5), SM with associated hematologic neoplasm (n=17), aggressive SM (ASM, n=9), and mast cell leukemia (n=4). We measured sFcɛRI levels at diagnosis and during follow-up and established correlations with the SM variant, prognostic parameters, and survival. Moreover, we assessed sFcɛRI effects on proliferation of neoplastic mast cells and IgE-dependent activation and histamine release in basophils obtained from SM patients. Compared to healthy controls, sFcεRI levels were within normal range in most patients with CM and ISM, whereas in most patients with advanced SM, especially those with ASM, increased sFcεRI levels were detected. Moreover, we found that a clearly elevated sFcεRI level in SM correlates with poor survival and a lower risk of vascular instability. sFcεRI levels did not correlate with serum tryptase levels, total IgE levels, or the presence of hereditary alpha-tryptasemia. In in vitro experiments, sFcεRI suppressed anti-IgE-induced CD63-expression and histamine release in basophils and growth of neoplastic mast cells. sFcεRI is often elevated in patients with advanced SM and acts as negative-regulator of growth and activation of neoplastic mast cells.