THE ALPHA-FORM OF HUMAN TRYPTASE IS THE PREDOMINANT TYPE PRESENT IN BLOOD AT BASE-LINE IN NORMAL SUBJECTS AND IS ELEVATED IN THOSE WITH SYSTEMIC MASTOCYTOSIS

Tryptase, a protease produced by all mast cells, was evaluated as a cl inical marker of systemic mastocytosis, Two sandwich immunoassays were evaluated, one which used the mAb G5 for capture, the other which use d B12 for capture, The B12 capture assay measured both recombinant alp ha- and beta-tryptase, whereas the G5 capture assay measured primarily recombinant beta-tryptase. G5 binds with low affinity to both recombi nant alpha-tryptase and tryptase in blood from normal and nonacute mas tocytosis subjects, and binds with high affinity to recombinant beta-t ryptase, tryptase in serum during anaphylaxis, and tryptase stored in mast cell secretory granules, B12 recognizes all of these forms of try ptase with high affinity, As reported previously, during systemic anap hylaxis in patients without known mastocytosis, the ratio of B12- to G 5-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. Van Der Linden J. Clin. Immunol. 14:190-204), In this rep ort, most mastocytosis patients with systemic disease have B12-measure d tryptase levels that are elevated(> 20 ng/ml) and are at least 10-fo ld greater than the corresponding G5-measured tryptase level, Most of those subjects with B12-measured tryptase levels of < 20 ng/ml had onl y cutaneous manifestations. The B12 assay for alpha-tryptase and beta- tryptase, particularly when performed in conjunction with the G5 assay for beta-tryptase, provides a more precise measure of mast cell invol vement than currently available assessments, a promising potential scr eening test for systemic mastocytosis and may provide an improved mean s to follow disease progression and response to therapy.