Abstract：
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.
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. 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.
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. 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.
摘要：
目的：概述目前对人类类胰蛋白酶遗传变异性的理解，并总结文献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。
结果：人们越来越认识到类胰蛋白酶基因组成，特别是常见的遗传性状遗传性α-胰蛋白酶血症（HαT），影响临床过敏。HαT一直与克隆性肥大细胞疾病（MCD）相关，并且在这些患者中也与更频繁的过敏反应相关。以及没有发现过敏触发因素的患者，特别是特发性过敏反应。此外,在回顾性和前瞻性研究中,膜翅目毒液过敏患者中更严重的过敏反应与HαT相关.α-类胰蛋白酶编码基因拷贝的相对数量增加，即使没有HαT,也与全身性肥大细胞增多症有关，并已显示与肥大细胞介导的对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。HαT是人类中天然存在的α-类胰蛋白酶过表达模型。增加的相对α-类胰蛋白酶表达改变了立即的超敏反应症状，并与更频繁和严重的肥大细胞介导的反应有关。表面上是由于α/β-类胰蛋白酶异四聚体的产生增加。
结果：人们越来越认识到类胰蛋白酶基因组成，特别是常见的遗传性状遗传性α-胰蛋白酶血症（HαT），影响临床过敏。HαT一直与克隆性肥大细胞疾病（MCD）相关，并且在这些患者中也与更频繁的过敏反应相关。以及没有发现过敏触发因素的患者，特别是特发性过敏反应。此外,在回顾性和前瞻性研究中,膜翅目毒液过敏患者中更严重的过敏反应与HαT相关.α-类胰蛋白酶编码基因拷贝的相对数量增加，即使没有HαT,也与全身性肥大细胞增多症有关，并已显示与肥大细胞介导的对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。HαT是人类中天然存在的α-类胰蛋白酶过表达模型。增加的相对α-类胰蛋白酶表达改变了立即的超敏反应症状，并与更频繁和严重的肥大细胞介导的反应有关。表面上是由于α/β-类胰蛋白酶异四聚体的产生增加。
