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ORIGINAL RESEARCH article

Front. Allergy
Sec. Genetics and Epidemiology
Volume 5 - 2024 | doi: 10.3389/falgy.2024.1461359

Hereditary alpha Tryptasemia: Elevated Tryptase, Female Sex, Thyroid Disorders and Anaphylaxis

Provisionally accepted
Viktoria Puxkandl Viktoria Puxkandl 1,2*Stefan Aigner Stefan Aigner 1Wolfram Hötzenecker Wolfram Hötzenecker 1,2Sabine Altrichter Sabine Altrichter 1,2,3,4
  • 1 Medical school, Johannes Kepler University of Linz, Linz, Austria
  • 2 Department for Dermatology and Venerology, Kepler University Hospital, Linz, Austria
  • 3 Institute of Allergology, Charité University Medicine Berlin, Berlin, Baden-Württemberg, Germany
  • 4 Fraunhofer Institute for Translational Medicine and Pharmacology, Hamburg, Hamburg, Germany

The final, formatted version of the article will be published soon.

    Introduction: The clinical significance of elevated baseline serum tryptase (BST) in the absence of mast cell disorders or allergic reactions has long remained unclear. Recently, a genetic variation of the TPSAB1 gene, which among others encodes for alpha tryptase has been reported and named Hereditary Alpha Tryptasemia (HaT). HaT has been linked to various manifestations, including severe allergic reactions. However, clinical studies are limited. Here, we aim to determine HaT prevalence and characterize its clinical manifestations in patients at a specialized allergy center. Methods: From January 2022 to December 2023, patients with at least once elevated BST were screened for HaT at the outpatient clinic. A control group included patients with a history of anaphylaxis undergoing specific hymenoptera immunotherapy. TPSAB1 copy numbers, BST levels, and clinical parameters were assessed and analyzed. Results: Of 47 patients with elevated BST (≥11.4µg/l), 93% showed increased TPSAB1 copy numbers. Individuals diagnosed with HaT displayed a BST range between 12.3 µg/l to 28.4 µg/l, with 84.1% associated with TPSAB1 duplication and 15.9% with triplication. HaT predominated in females (86.4%) and was associated with thyroid disease (27.3%). Over half had a history of anaphylaxis (54.5%), mainly low-grade. Discussion: In patients with elevated BST but no mastocytosis, the most likely cause of elevated BST is an increase in the copy number of the TPSAB1 gene. A heightened risk of anaphylaxis should be considered. Further research is needed to explore the female predominance and the emerging link with thyroid disease.

    Keywords: Hereditary alpha Tryptasemia: Elevated Tryptase, Female sex, Thyroid Disorders HaT: Tryptase, thyroid disorders, Anaphylaxis Anaphylaxis, Hereditary alpha tryptasemia, Thyroid Gland, TPSAB1 Allakos

    Received: 08 Jul 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Puxkandl, Aigner, Hötzenecker and Altrichter. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Viktoria Puxkandl, Medical school, Johannes Kepler University of Linz, Linz, Austria

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