Purpose of Review

To provide an overview on the current understanding of genetic variability in human tryptases and summarize the literature demonstrating the differential impact of mature tryptases on mast cell–mediated reactions and associated clinical phenotypes.

Recent Findings

It is becoming increasingly recognized that tryptase gene composition, and in particular the common genetic trait hereditary alpha-tryptasemia (HαT), impacts clinical allergy. HαT has consistently been associated with clonal mast cell disorders (MCD) and has also been associated with more frequent anaphylaxis among these patients, and patients in whom no allergic trigger can be found, specifically idiopathic anaphylaxis. Additionally, more severe anaphylaxis among Hymenoptera venom allergy patients has been linked to HαT in both retrospective and prospective studies. An increased relative number of α-tryptase-encoding gene copies, even in the absence of HαT, has also been associated with systemic mastocytosis and has been shown to positively correlate with the severity of mast cell–mediated reactions to vibration and food. These findings may be due to increased generation of α/β-tryptase heterotetramers and differences in their enzymatic activity relative to β-tryptase homotetramers.

Summary

HαT is a naturally occurring overexpression model of α-tryptase in humans. Increased relative α-tryptase expression modifies immediate hypersensitivity symptoms and is associated with more frequent and severe mast cell–mediated reactions, ostensibly due to increased α/β-tryptase heterotetramer production.

中文翻译：

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α-类胰蛋白酶作为肥大细胞介导反应的风险调节因子

审查目的

概述目前对人类类胰蛋白酶遗传变异性的理解，并总结证明成熟类胰蛋白酶对肥大细胞介导的反应和相关临床表型的不同影响的文献。

最近的发现

人们越来越认识到，类胰蛋白酶基因组成，特别是常见遗传性状遗传性 α-类胰蛋白酶血症 (HαT)，会影响临床过敏。HαT 一直与克隆性肥大细胞疾病 (MCD) 相关，并且还与这些患者以及未发现过敏触发因素的患者（特别是特发性过敏反应）中更频繁的过敏反应相关。此外，回顾性和前瞻性研究表明，膜翅目毒液过敏患者中更严重的过敏反应与 HαT 相关。即使在不存在 HαT 的情况下，α-类胰蛋白酶编码基因拷贝的相对数量增加也与系统性肥大细胞增多症相关，并且已被证明与肥大细胞介导的振动和食物反应的严重程度呈正相关。这些发现可能是由于 α/β-类胰蛋白酶异四聚体的产生增加以及它们的酶活性相对于 β-类胰蛋白酶同四聚体的差异。

概括

HαT 是人类自然发生的 α-类胰蛋白酶过表达模型。相对α-类胰蛋白酶表达的增加可改善即时过敏症状，并与更频繁和更严重的肥大细胞介导的反应相关，表面上是由于α/β-类胰蛋白酶异四聚体的产生增加。