Mast cells and tryptase. Modern aspects

The present review considers the role of mast cells (MC) and tryptase levels in various pathological conditions in children and adults. The main causes of hypertryptasemia are presented, as well as a list of the most important stimuli that can cause activation of MC. Cliical allergologists should focus their clinical practice on the patients with anaphylaxia and suspected MC activation syndromes. Moreover, hypertryptasemia (> 20 ng/ml) is considered an additional diagnostic criterion for systemic mastocytosis, according to the WHO recommendations. As a rule, the level of tryptase is constantly elevated in most patients with systemic mastocytosis, whereas it is undergo changes in acute IgE-mediated hypersensitivity reactions. In cases of anaphylaxia, tryptase concentration should be determined in the patients during the first hours following onset of acute allergic reaction, and 24-48 hours later. Recommendations are given for determining tryptase levels in blood serum of the patients (basal and peak values), and algorithms are provided for usage of these indexes in various diseases. The article also provides the assessed threshold values of tryptase when diagnosing anaphylaxia, MC activation syndromes, and a novel disorder – alpha-tryptasemia. In the diagnosis of hereditary alpha-tryptasemia, as well as MC activation syndromes (primary and secondary), clinical manifestations in the patient and time dynamics of tryptase levels should be taken into account. The accumulated experience allowed to consider, first of all, frequency of severe allergic reactions (most often as anaphylaxia) in the patients with suspected MC activation syndromes. The syndrome of MC activation is characterized by excessive release of their granule contents without signs of clonal proliferation, which in many cases may be due to gene allele duplication, especially, TPSAB1 α-tryptase gene. For patients with hereditary alpha-tryptasemia, the most characteristic manifestations are represented by vegetative-vascular dystonia (orthostatic tachycardia), joint hypermobility, etc. Hence, determination of tryptase level (especially in time course) should be given more attention in the practice of clinicians. Difficulties with interpretation of the results arise in cases when tryptase concentration remains within normal range (up to 11.4 ng/ml), and the patient has clinically evident mastocytosis, or MC activation syndromes. If the patient has a history of anaphylaxia, especially after bites of hymenoptera insects, the TC activation syndromes should be excluded.

1. Akin C. Mast cell activation syndromes. J. Allergy Clin. Immunol., 2017, Vol. 140, no. 2, pp. 349-55.

2. Arber D.A., Orazi A., Hasserjian R., Thiele J., Borowitz M.J., Le Beau M.M., Bloomfield C.D., Cazzola M., Vardiman J.W. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 2016, Vol. 127, no. 20, pp. 2391-2405.

3. Balzar S., Chu H.W., Strand M., Wenzel S. Relationship of small airway chymase-positive mast cells and lung function in severe asthma. Am. J. Respir. Crit. Care Med., 2005, Vol. 171, no. 5, pp. 431-439.

4. Bischoff S. Mast cells in gastrointestinal disorders. Eur. J. Pharmacol., 2016, Vol. 778, pp. 139-145.

5. Boyden S.E., Desai A., Cruse G., Young M.L., Bolan H.C., Scott L.M., Eisch A.R., Long R.D., Lee C.C., Satorius C.L., Pakstis A.J., Olivera A., Mullikin J.C., Chouery E., Mégarbané A., Medlej-Hashim M., Kidd K.K., Kastner D.L., Metcalfe D.D., Komarow H,D. Vibratory urticaria associated with a missense variant in ADGRE2. N. Engl. J. Med., 2016, Vol. 374, pp. 656-663.

6. Broesby-Olsen S. Mastocytosis: urticaria pigmentosa and mastocytosis in the skin. Global Atlas of Skin Allergy, 2019, pp. 177-179.

7. Cruse G., Metcalfe D., Olivera A. Functional deregulation of KIT: link to mast cell proliferative diseases and other neoplasms. Immunol. Allergy Clin. North Am., 2014, Vol. 34, no. 2, pp. 219-237.

8. Elishmereni M., Bachelet I., Nissim Ben-Efraim A., Mankuta D. Levi-Schaffer F. Interacting mast cells and eosinophils acquire an enhanced activation state in vitro. Allergy, 2013, Vol. 68, pp. 171-179.

9. Marshall J., Portales-Cervantes L., Leong E. Mast cell responses to viruses and pathogen products. Int. J. Mol. Sci., 2019, Vol. 20, no. 17, 4241. doi: 10.3390/ijms20174241.

10. Maurer M., Köberle M., Metz M., Biedermann T. Mast cells: Promoters of health and modulators of disease. J. Allergy Clin. Immunol., 2019, Vol. 144, no. 4S, pp. S1-S3.

11. Metcalfe D.D., Peavy R.D., Gilfillan A.M. Mechanisms of mast cell signaling in anaphylaxis. J. Allergy Clin. Immunol., 2009, Vol. 124, no. 4, pp. 639-646.

12. Normansell R., Walker S., Milan S.J., Walters E.H., Nair P. Omalizumab for asthma in adults and children. Cochrane Database Syst. Rev., 2014, no. 1, CD003559. doi: 10.1002/14651858.CD003559.pub4.

13. Theoharides T., Valent P., Akin C. Mast cells, mastocytosis, and related disorders. N. Engl. J. Med., 2015, Vol. 373, no. 2, pp. 163-172.

14. Weller K., Ohanyan T., Hawro T., Ellrich A., Sussman G., Koplowitz J., Gimenez-Arnau A.M., PevelingOberhag A., Staubach P., Metz M., Maurer M. Total IgE levels are linked to the response of chronic spontaneous urticaria patients to omalizumab. Allergy, 2018, Vol. 73, no. 12, pp. 2406-2408.

15. Wilcock A., Bahri R., Bulfone-Paus S., Arkwright P. Mast cell disorders: From infancy to maturity. Allergy, 2019, Vol. 74, no. 1, pp. 53-63.

16. Valent P. Diagnosis and management of mastocytosis: an emerging challenge in applied hematology. Hematology Am. Soc. Hematol. Educ. Program, 2015, Vol. 2015, pp. 98-105.