The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis.

Abstract

Tryptase, a protease produced by all mast cells, was evaluated as a clinical marker of systemic mastocytosis. Two sandwich immunoassays were evaluated, one which used the mAb G5 for capture, the other which used B12 for capture. The B12 capture assay measured both recombinant a-and .-tryptase, whereas the G5 capture assay measured primarily recombinant f8-tryptase. G5 binds with low affinity to both recombinant c-tryptase and tryptase in blood from normal and nonacute mastocytosis subjects, and binds with high affinity to recombinant ,B-tryptase, tryptase in serum during anaphylaxis, and tryptase stored in mast cell secretory granules. B12 recognizes all of these forms of tryptase with high affinity. As reported previously, during systemic anaphylaxis in patients without known mastocytosis, the ratio of B12-to G5-measured tryptase was always < 5 and approached unity (Schwartz L. B., T. R. Bradford, C. Rouse, A.-M. Irani, G. Rasp, J. K. Van der Zwan and P.-W. G. . In this report, most mastocytosis patients with systemic disease have B12-measured tryptase levels that are elevated (> 20 ng/ml) and are at least 10-fold greater than the corresponding G5-measured tryptase level. Most of those subjects with B12-measured tryptase levels of < 20 ng/ml had only cutaneous manifestations. The B12 assay for a-tryptase and ,3-tryptase, particularly when performed in conjunction with the G5 assay for j8-tryptase, provides a more precise measure of mast cell involvement than currently available assessments, a promising potential screening test for systemic mastocytosis and may provide an improved means to follow disease progression and response to therapy. (J. Clin. Invest. 1995Invest. . 96:2702Invest. -2710

Does β-Hexosaminidase Function Only as a Degranulation Indicator in Mast Cells? The Primary Role of β-Hexosaminidase in Mast Cell Granules

“…Mast cells contain a large amount of enzymes in the granules (25,26), particularly proteases (27). These enzymes are known to be involved in inflammation (28)(29)(30) and host defense against bacteria (31, 32).…”

Human Tryptases α and β/II Are Functionally Distinct Due, in Part, to a Single Amino Acid Difference in One of the Surface Loops That Forms the Substrate-binding Cleft

“…While normal human basophils contain a small amount of tryptase ␣ protein (17) and mRNA (18), substantial numbers of tryptase ␣ ϩ cells have been found in the blood of patients with asthma, chronic allergies, or adverse drug reactions (19). The level of tryptase ␣ is also elevated in the sera of patients with systemic mastocytosis (20). Thus, whether or not tryptase ␣ is a functional neutral protease in humans is of critical importance.…”

Tryptase haplotype in mastocytosis: Relationship to disease variant and diagnostic utility of total tryptase levels

“…Tryptase levels were measured by immunoassay, using G5 and G4 monoclonal anti-tryptase antibodies to capture mature (mainly β) and total tryptase (combination of α, and β protryptases and mature [primarily β] tryptases) respectively, as described [12]. Direct ELISA measurement of α protryptase is not currently possible as there is no antibody that distinguishes α from β pro or mature tryptases.…”