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Mast cell activation in the context of elevated basal serum tryptase: genetics and presentations

  • Anaphylaxis and Drug Allergy (DA Khan and M Castells, Section Editors)
  • Published:
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Abstract

Purpose of Review

To describe inherited and acquired genetic variants and clinical entities associated with increased basal serum tryptase (BST), distinguish these levels from those which acutely rise due to mast cell activation, and finally to characterize the association between chronically elevated basal serum tryptase and episodic mast cell activation.

Recent Findings

Hereditary alpha-tryptasemia is a commonly inherited genetic cause for basally elevated serum tryptase and explains elevated BST in many individuals who do not have evidence of clonal myeloid or mast cell disease. When clonal myeloid disease is present, BST may be elevated and can be a biomarker of a number of disparate disorders of the myeloid compartment.

Summary

Elevated BST is most commonly caused by hereditary alpha tryptasemia but may also be indicative of clonal myeloid disease. Clinical reports suggest that elevated BST is associated with increased risk for more severe systemic allergic reactions to a number of eliciting agents and exposures. Additional studies are needed to determine the role that inherited or acquired genetic variants associated with elevated BST and clonal or non-clonal myeloid diseases may play in these reactions.

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Abbreviations

HαT:

Hereditary alpha tryptasemia

BST:

Basal serum tryptase

PAF:

Platelet activating factor

EMR2:

EGF-like module-containing mucin-like hormone receptor-like 2

TPSAB1 :

Tryptase alpha/beta 1 gene

TPSB2 :

Tryptase beta 2 gene

GBA:

Glucosylceramidase

GATA2:

GATA binding protein 2

JAK2 :

Janus kinase 2 gene

STAT5b:

Signal transducer and activator of transcription 5b

KIT :

KIT proto-oncogene receptor tyrosine kinase

MMAS:

Monoclonal mast cell activation

PAR:

Protease activated receptor

FIP1L1/PDGFRA :

FIP1-like-1/platelet-derived growth factor receptor-α fusion gene

HES:

Hypereosinophilic syndrome

AML:

Acute myeloid leukemia

CML:

Chronic myeloid leukemia

JMML:

Juvenile myelomonocytic leukemia

CsU:

Chronic spontaneous urticaria

ISM:

Indolent systemic mastocytosis

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Funding

This research was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, NIH.

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  1. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Paneez Khoury

  2. Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Building 10, Room 11N240, MSC 1889, Bethesda, MD, 20892, USA

    Jonathan J. Lyons

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Khoury, P., Lyons, J.J. Mast cell activation in the context of elevated basal serum tryptase: genetics and presentations. Curr Allergy Asthma Rep 19, 55 (2019). https://doi.org/10.1007/s11882-019-0887-x

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