Distinct plasma biomarkers confirm the diagnosis of mastocytosis and identify increased risk of anaphylaxis.

ABSTRACT Background Mastocytosis encompasses a heterogenous group of disorders characterized by accumulation of clonal mast cells (MCs) in the skin and/or internal organs. Patients typically present with a broad variety of recurrent mediator-related clinical symptoms, including severe anaphylaxis. However, not all patients with mastocytosis experience anaphylactic reactions. Objective We sought to identify disease specific biomarkers in plasma, that could be used to predict mastocytosis patients with increased risk of anaphylaxis. Methods Nineteen patients (≥18 years) and two control groups (11 subjects with allergic asthma, and 13 healthy volunteers without history of atopy) were recruited. In total, 248 plasma proteins were analyzed by Proximity Extension Assay (PEA) using Olink Proseek Multiplex panels. Results We identified four novel proteins, in addition to tryptase, E-selectin, Adrenomedullin, T cell immunoglobulin and mucin domain 1, and CUB domain-containing protein 1/CD138 to be significantly increased in mastocytosis compared to both asthma and healthy controls. Further, we investigated whether we could discriminate between mastocytosis patients with or without anaphylaxis. In addition to tryptase, we identified three novel proteins; i.e., Allergin-1, pregnancy-associated plasma protein-A and Galectin-3, with significantly different levels in mastocytosis patients with anaphylaxis compared to those without anaphylaxis. Conclusion Newly identified proteomic biomarkers may be used to predict mastocytosis patients with increased risk of anaphylaxis. Clinical Implications Newly detected proteomic biomarkers may have the potential to improve diagnosis of mastocytosis and increased risk of anaphylaxis.