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

Abstract

The soluble alpha chain of FcεRI (sFcεRI) is released during receptor cross-linking on mast cells (MCs) and serves as an acceptor site for circulating IgE. Recent data suggest that sFcεRI counteracts MC activation in allergic patients. We measured the levels of sFcεRI and its effect in cutaneous mastocytosis and systemic mastocytosis (SM). sFcεRI levels were quantified by ELISA in 114 patients with mastocytosis, including cutaneous mastocytosis (n = 12), indolent SM (n = 67), smoldering SM (n = 5), SM with associated hematologic neoplasm (n = 17), aggressive SM (n = 9), and MC leukemia (n = 4). We measured sFcεRI levels at diagnosis and during follow-up and established correlations with the SM variant, prognostic parameters, and survival. Moreover, we assessed sFcεRI effects on proliferation of neoplastic MCs 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 cutaneous mastocytosis and indolent SM, whereas in most patients with advanced SM, especially those with aggressive SM, 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 α-tryptasemia. In in vitro experiments, sFcεRI suppressed anti-IgE-induced CD63 expression and histamine release in basophils and growth of neoplastic MCs. sFcεRI is often elevated in patients with advanced SM and acts as negative regulator of growth and activation of neoplastic MCs.