Tryptase

Immunology

Description

Tryptase is a serine esterase characterised as a tetramer with a molecular weight of 144,000 Daltons and exists in an alpha and beta form. The mature tetrameric beta form is stored within the mast cell granules. The enzyme consists of four non-covalently bound subunits, 2 alpha and 2 beta with each subunit having one active enzymatic site [2]. The tetrameric form occurs in acidic conditions in the presence of heparin. Monomeric components occur in alkaline conditions. This assay measures total tryptase and does not differentiate between the alpha or beta types. Mast cells play a key role in allergic reactions and increase in numbers under inflammatory conditions. When activated, they degranulate and release a variety of mediators that lead to the signs and symptoms of allergic reactions, such as systemic anaphylaxis. These mediators include tryptase and histamine [3]. Mast cells bear high affinity receptors for the Fc portion of IgE and linking two or more receptor bound IgE antibodies by allergen stimulates them to degranulate. Mast cells may also be activated by non-IgE mechanisms involving complement anaphylatoxins (C3a and C5a) or opiates. Isolated tryptase levels may be of value in the assessment of allergic disorders and mast cell syndromes (mastocytosis). Systemic mastocytosis is associated with mast cell hyperplasia in skin lesions (urticaria pigmentosa), liver, spleen, lymph nodes and bone marrow. In a study of tryptase levels in subjects with biopsy diagnosed mastocytosis, most of those with systemic mastocytosis had levels of total tryptase >20 ug/L [4].

About 5% of the population have a tryptase value >8 ug/L. 90% of these individuals have an extra TPSAB1 gene copy number leading to increased production of alpha tryptase and a resulting increase in total tryptase. Hereditary alphatryptasaemia (HAT) individuals can have an increased frequency and severity of anaphylaxis and is found more frequently in a mastocytosis population compared to a normal population [8].

Indications

Anaphylaxis. Mast cell syndromes such as mastocytosis.

Sample Type

2mL Plasma (EDTA 5mL tube or Lithium Heparin 7mL tube) or 2mL Serum (Gel 5mL Yellow tube). Requests from outside Sheffield: Transport at ambient temperature via Royal Mail or Courier.

Reference Range

Basal levels are in the range of 2 to 14ug/L, with peak levels of more than 40ug/L being associated with anaphylaxis. Reference range established in house.

Turnaround Time

Within 5 days

Testing Frequency

Daily

External Notes

Interpretation of the results can only be given by a Clinical Scientist/ Medical Consultant/Medical Officer.

References

Sargur R, et al. Raised tryptase without anaphylaxis or mastocytosis: heterophilic antibody interference in the serum tryptase assay. Clin Exp Imm. 2011. 163(3):339-345. [Ref 1]Caughey GH. Tryptase genetics and anaphylaxis. J Allergy Clin Immunol. 2006. 117(6):1411-1414. [Ref 1]Payne V and Kam PC. Mast cell tryptase: a review of its physiology and clinical significance. Anaesthesia. 2004. 59(7):695-703. [Ref 2]Schwartz LB. Clinical utility of tryptase levels in systemic mastocytosis and associated hematological disorders. Leukaemia research. 2001. 25:553-562. [Ref 3].Afrin LB. Presentation, diagnosis and management of mast cell activation syndrome. Mast cells. 2013. Chapter 6, pp 155-231. [Ref 4]Akin C, Valent P and Metcalf D. Mast cell activation syndrome: Proposed diagnostic criteria: Towards a global classification for mast cell disorders. J Allergy Clin Immunol. 2010. 126(6): 1099-1111. [Ref 5].Valent P, Akin C, Escribano L, et al. Standards and standardisation in mastocytosis: Consensus statements on dignostics, treatment recommendations and response criteria. Euro J Clinn Invest. 2007. 37: 435-453. [Ref 6].NICE Clinical Guideline 134 (CG134). Anaphylaxis: Assessment to confirm an anaphylactic episode and the decision to refer after emergency treatment for a suspected anaphylactic episode. 2011. [Ref 7]. Chollet MB and Akin C. Hereditary alpha tryptasemia is not associated with specific clinical phenotypes. J Allergy Clin Immunol. 2022. 149(2):728-735. [Ref 8].

Your contact for this test

Clare Del-Duca BSc (Hons) Biomedical Science, MSc Pathological Science

Laboratory Manager - Immunology and Protein Reference Unit

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Tryptase