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Alpha-Tryptase as a Risk-Modifying Factor for Mast Cell–Mediated Reactions

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Abstract

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.

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Data Availability

No datasets were generated or analysed during the current study.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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  1. Division of Allergy & Immunology, Department of Medicine, University of California San Diego, La Jolla, CA, USA

    Hannah Shin & Jonathan J. Lyons

  2. Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA

    Jonathan J. Lyons

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HS and JJL both conceived, authored, edited, and reviewed this manuscript.

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Shin, H., Lyons, J.J. Alpha-Tryptase as a Risk-Modifying Factor for Mast Cell–Mediated Reactions. Curr Allergy Asthma Rep 24, 199–209 (2024). https://doi.org/10.1007/s11882-024-01136-y

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