Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Curr Opin Allergy Clin Immunol. 2020 Oct;20(5):431-437. doi: 10.1097/ACI.0000000000000678.
To discuss the association between the common dominantly inherited genetic trait hereditary alpha-tryptasemia (HαT) and hymenoptera venom-induced anaphylaxis (HVA).
Elevated BST has been correlated with more severe systemic anaphylaxis in humans in a number of settings - most notably in HVA. Clonal mast cell disease, in particular, systemic mastocytosis, is frequently associated with elevated BST, and is a major risk factor for severe HVA. However, clonal mast cell diseases are believed to be rare, whereas HVA is relatively more common. HαT affects an estimated 3-5% of Western populations and is the common cause for elevated BST in these individuals. An association between HαT and severe HVA, as well as clonal mast cell disease has recently been demonstrated wherein this trait modifies reaction severity in venom allergic individuals. A mechanism underlying this association has been proposed through the identification of naturally occurring heterotetrameric tryptases and characterization of their unique physical attributes.
Here we discuss the long-standing association between elevated BST and HVA severity, how HαT fits into this landscape, and review the clinical and mechanistic evidence that supports HαT as a modifier of HVA.
探讨常见的显性遗传性遗传特征遗传性α-色氨酸血症(HαT)与膜翅目毒液诱导的过敏反应(HVA)之间的关联。
在许多情况下,包括 HVA,升高的 BST 与人类更严重的全身性过敏反应相关联-尤其是在 HVA 中。克隆性肥大细胞疾病,特别是全身性肥大细胞增多症,常与升高的 BST 相关联,是严重 HVA 的主要危险因素。然而,人们认为克隆性肥大细胞疾病很少见,而 HVA 则相对更常见。HαT 估计影响了 3-5%的西方人群,是这些个体中 BST 升高的常见原因。最近已经证明,HαT 与严重的 HVA 和克隆性肥大细胞疾病之间存在关联,这种特征改变了过敏个体的反应严重程度。通过鉴定天然存在的异四聚体类胰蛋白酶并对其独特的物理特性进行表征,提出了这种关联的机制。
在这里,我们讨论了升高的 BST 与 HVA 严重程度之间的长期关联,HαT 如何适应这一领域,并回顾支持 HαT 作为 HVA 修饰因子的临床和机制证据。