The Normal Range of Baseline Tryptase Should Be 1 to 15 ng/mL and Covers Healthy Individuals With HαT

Reversible Elevation of Tryptase Over the Individual's Baseline: Why is It the Best Biomarker for Severe Systemic Mast Cell Activation and MCAS?

“…The basal tryptase level is remarkably stable over time in individual healthy donors provided that no underlying disease associated with MC activation or MC expansion is present [ 16 , 17 , 18 •]. Moreover, in contrast to many other MC-derived mediators (histamine, PGD2, heparin, others), tryptase is a biologically stable protein that is not degraded, removed, or de-activated by changes in temperature, by other plasma proteins, or by short-term storage.…”

“…However, the basal serum tryptase level varies among healthy individuals, depending on the genetic background, sex, age, kidney function, and presence of an underlying disease associated with MC expansion and/or activation [ 16 , 17 , 18 •].…”

“…The normal serum tryptase level ranges between 0 and 15 ng/mL in healthy adults of Caucasian origin [ 18 •, 19 – 21 ]. In those with HαT, tryptase levels are either within normal range or are elevated (> 15 ng/mL), depending on the number of extra-copies of the TPSAB1 gene, and independent of the symptoms recorded or the presence of co-morbidities.…”

“…In those with HαT, tryptase levels are either within normal range or are elevated (> 15 ng/mL), depending on the number of extra-copies of the TPSAB1 gene, and independent of the symptoms recorded or the presence of co-morbidities. When excluding HαT carriers from the pool of healthy controls, the normal basal serum tryptase level amounts to approximately 0–11.4 ng/mL [ 16 , 17 , 18 •]. However, most HαT carriers are asymptomatic or have non-specific co-morbidities not attributable to MC activation or tryptase, so that these individuals must be included in calculating the normal range of serum tryptase levels [ 36 ].…”

“…Whereas the mature tryptase proteins are preferentially stored in the heparin-containing, secretory metachromatic granules of MC, the enzymatically inactive precursor (pro) forms of tryptase, are released continuously by resting cells, independent of the maturation stage of MC, the tissue and organ site, and the underlying pathology [ 10 , 11 , 12 •, 14 , 15 ]. As a result of steady-state release of the enzyme and its chemical stability under various conditions, the basal serum tryptase level in individual (healthy) donors is remarkably consistent, although slight variations (fluctuations) of the individual baseline have been described, especially in individuals with hereditary alpha tryptasemia (HαT), a condition leading to elevated baseline serum tryptase levels due to multiple copy numbers of TPSAB1 encoding alpha tryptase [ 16 , 17 , 18 •]. The basal serum tryptase level can also be elevated in various reactive processes and in diverse malignancies but usually remains stable in individual patients when tested over time, unless the malignancy progresses or is successfully treated [ 19 – 22 , 23 •, 24 ].…”