Translational studies in allergic reactions and inflammation

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

In Fiscal Year (FY) 2022, we continued to advance our understanding of acquired and inherited genetic changes that promote mast cell reactivity, anaphylaxis, and allergic inflammation. Foremost among the advances we reported this FY, was a manuscript features in the JACI as an Editor's Choice in which we led an international collaboration demonstrating that hereditary alpha-tryptasemia (HaT) - a genetic trait first discovered by our laboratory in 2016 - is a heritable risk factor for severe anaphylaxis and modifier of clonal and non-clonal mast cell disorders where it augments symptom frequency and severity. And validated the link to venom anaphylaxis severity in a second prospective study with one of our international collaborators. In a second multi-center collaboration led by our group, that was also featured as an Editor's Choice in the JACI, we report unique immunologic changes seen in the gut mucosae of individuals with hereditary alpha-tryptasemia that included evidence of gut barrier disruption and mast cell activation which may contribute to certain clinical phenotypes observed in symptomatic individuals with this trait. We also refined some of the phenotypes and genetics associated with HaT demonstrating that HaT can modify clinical phenotypes of patients with congenital hypermobility disorders, but is not increased in prevalence among those with them, and that copy number loss can also occur at TPSAB1. Beyond these advances, we clarified baseline variability of serum tryptase levels and redefined what a threshold increase is that would be associated with immediate hypersensitivity reactions.