Translational studies in allergic reactions and inflammation

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In Fiscal Year (FY) 2020, we continued to advance our understanding of acquired and inherited genetic changes that promote mast cell reactivity and anaphylaxis. Through an ongoing collaboration with the Schwartz lab at Virginia Commonwealth University (VCU), we demonstrated a putative mechanism which may underly certain symptoms associated with hereditary alpha tryptasemia - a common genetic trait associated with mast cell reactivity, that we first reported in 2016. In our recent publication in J Exp Med, we demonstrate the natural occurrence of tryptase heterotetramer for the first time, and characterize their unique physiochemical properties that lead to increased mast cell reactivity to vibration. We also reported the first case series describing the clinical response of patients with this trait to the monoclonal antibody omalizumab. Finally, in an international collaboration with researchers from Italy and Slovenia, we led an effort to validate the heritable risk for severe anaphylaxis to Hymenoptera envenomation, as well as severe anaphylaxis among individuals with mast cell disorders recently published in J Allergy Clin Immunol.