Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Massachusetts.
Ann Allergy Asthma Immunol. 2021 Jun;126(6):655-660. doi: 10.1016/j.anai.2021.01.016. Epub 2021 Jan 17.
Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait characterized by multiple copies of the alpha-tryptase gene at the TPSAB1 locus. Previously described symptomatology involves multiple organ systems and anaphylaxis. The spectrum of mast cell activation symptoms is unknown, as is its association with specific genotypes.
To describe clinical, laboratory, and genetic characteristics of patients referred for the evaluation of mast cell activation-related symptoms and genotype-confirmed HαT.
We retrospectively describe clinical characteristics, baseline tryptase, and tryptase genotype in 101 patients. Patients were referred for mast cell activation-related symptoms and underwent genotyping to confirm diagnosis of HαT.
Of 101 patients, 80% were female with average tryptase of 17.2 ng/mL. Tryptase was less than 11.4 ng/mL in 8.9% and greater than 20 ng/mL in 22.3% (range 6.2-51.3 ng/mL). KIT D816V mutation was negative in all subjects tested. 2α:3β was the most common genotype but did not correlate with tryptase levels. Unprovoked anaphylaxis was noted in 57% of the subjects with heterogeneous genotypes. Most common symptoms include gastrointestinal, cutaneous, psychiatric, pulmonary, cardiovascular, and neurologic. A total of 85% of patients were taking H- or H-antihistamines with partial symptom relief. Omalizumab was effective at suppressing anaphylaxis or urticaria in 94% of the patients.
HαT encompasses a broad range of baseline tryptase and should be considered in patients with symptoms of mast cell activation and tryptase levels greater than 6.2 ng/mL. Patients may present with complex symptomatology including cutaneous, gastrointestinal, neurologic, and psychiatric symptoms and anaphylaxis, some of which respond to omalizumab.
遗传性α-胰蛋白酶血症（HαT）是一种常染色体显性遗传特征，其特点是 TPSAB1 基因座上存在多个α-胰蛋白酶基因副本。以前描述的症状涉及多个器官系统和过敏反应。肥大细胞激活症状的范围尚不清楚，其与特定基因型的关系也不清楚。
描述因肥大细胞激活相关症状就诊并经基因确认为 HαT 的患者的临床、实验室和遗传特征。
我们回顾性描述了 101 例患者的临床特征、基线胰蛋白酶和胰蛋白酶基因型。患者因肥大细胞激活相关症状就诊并进行基因分型以确认 HαT 的诊断。
在 101 例患者中，80%为女性，平均胰蛋白酶为 17.2ng/mL。8.9%的患者胰蛋白酶小于 11.4ng/mL，22.3%的患者胰蛋白酶大于 20ng/mL（范围为 6.2-51.3ng/mL）。所有检测的 KIT D816V 突变均为阴性。2α:3β 是最常见的基因型，但与胰蛋白酶水平无关。具有异质基因型的 57%的患者出现自发性过敏反应。最常见的症状包括胃肠道、皮肤、精神、肺部、心血管和神经系统。85%的患者正在服用 H1 或 H2 抗组胺药，部分患者的症状有所缓解。奥马珠单抗对抑制过敏反应或荨麻疹有效，94%的患者有效。
HαT 涵盖了广泛的基线胰蛋白酶范围，应考虑在有肥大细胞激活症状和胰蛋白酶水平大于 6.2ng/mL 的患者中进行考虑。患者可能出现复杂的症状，包括皮肤、胃肠道、神经和精神症状以及过敏反应，其中一些对奥马珠单抗有反应。
