A team of researchers led by Dean D. Metcalfe, MD, described how to use the results of a serum tryptase test to diagnose and manage systemic mastocytosis (SM) and anaphylaxis, and published their findings in the Journal of Allergy and Clinical Immunology: In Practice.
Mast cell tryptase levels are important for the diagnosis and management of mast cell disorders such as SM. Research has shown that most people with high levels of serum tryptase also have increased germline copy number of the TPSAB1 gene, which encodes α-tryptase.
The presence of hereditary alpha-tryptasemia, ie high germline TPSAB1 gene copy number, should be evaluated when defining what constitutes an abnormal level of serum tryptase during the diagnosis of SM, the authors said.
“Advances in the understanding of tryptase genetics . . . have fundamentally changed the clinical interpretation of this biomarker,” wrote first author Jonathan J Lyons, MD, and the coauthors of the review.
Read more about the diagnosis of SM
The authors suggest that people with a baseline serum level of tryptase of more than 6.5 ng/mL be genotyped for TPSAB1 gene copy number to screen for hereditary alpha-tryptasemia.
In the next steps, the authors suggest that mechanistic studies should be performed to better understand the impact of differential TPSAB1 gene expression as well as basic genetic studies to characterize the genetic variability in the human population.
“We envision this knowledge will be incorporated not only into clinical practice but also anticipate an expanded role in clinical trial design for diseases associated with mast cells in the future,” they wrote.
Tryptase is a neutral protease that is selectively concentrated in the secretory granules of human mast cells and is a marker of mast-cell activation. Mastocytosis is a group of diseases characterized by excessive amounts of pathologic mast cells proliferating and accumulating in different tissues causing damage.
Lyons JJ, Greiner G, Hoermann G, Metcalfe DD. Incorporating tryptase genotyping into the workup and diagnosis of mast cell diseases and reactions. J Allergy Clin Immunol Pract. 2022;18(22):00489-5. doi:10.1016/j.jaip.2022.05.003