Translational studies in allergic reactions and inflammation

在2020财年，我们继续推进我们对促进肥大细胞反应和过敏反应的获得性和遗传性基因变化的理解。通过与弗吉尼亚联邦大学(VCU)施瓦茨实验室的持续合作，我们展示了一种可能的机制，它可能低估了与遗传性α-胰腺炎相关的某些症状--这是一种与肥大细胞反应相关的常见遗传特征，我们在2016年首次报道了这一现象。在我们最近发表在J Exp Med上的文章中，我们首次证明了类胰蛋白酶异四聚体的自然存在，并表征了它们独特的物理化学性质，导致肥大细胞对振动的反应性增加。我们还报告了第一个病例系列，描述了具有这种特征的患者对单抗奥马珠单抗的临床反应。最后，在与意大利和斯洛文尼亚研究人员的国际合作中，我们领导了一项工作，以验证膜翅目毒液严重过敏反应的可遗传风险，以及最近发表在J过敏性Clin免疫学杂志上的肥大细胞疾病患者的严重过敏反应风险。

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.