A research paper recently published in Frontiers in Allergy proposes rethinking the longstanding definition of “normal” basal serum tryptase (BST) levels when used to diagnose systemic mastocytosis (SM).
Traditionally, a BST level exceeding 20 nanograms per milliliter (ng/mL) has been considered a key sign of SM, but the researchers argue this fixed threshold doesn’t account for individual variability influenced by genetic and physiological factors.
“BST normal values have been established in the range of 1 to 11.5 ng/ml, maintaining a consistent level in healthy individuals due to the balance between storage and release from MCs [mast cells],” the study’s authors said. “However, several reasons other than SM can increase BST, including pregnancy, chronic kidney disease, other myeloid neoplasms and HαT.”
Hereditary alpha-tryptasemia (HαT), a genetic condition characterized by increased copy numbers of the TPSAB1 gene can cause elevated BST levels. People with HαT may have BST levels above the traditional threshold without having any symptoms of SM. On the other hand, some individuals affected by SM may have BST levels lower than 20 ng/mL, particularly if they lack the genetic variations associated with higher tryptase production.
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The researchers propose doctors consider individuals’ genetic backgrounds when interpreting BST levels, particularly the number of TPSAB1 gene copies. Doing so can help clinicians better distinguish between elevated BST levels due to benign genetic variations and those which actually signal SM. This could potentially prevent unnecessary invasive follow-up tests like bone marrow biopsies in individuals who don’t need them and lead to more accurate diagnoses.
The study authors call for more research to set clearer guidelines for tryptase levels based on genetics, and for improved access to genetic testing.
“A rational use of BST and genetic testing in the different clinical settings is the premise to balance the application of invasive diagnostics to the actual probabilities of underlying SM disorders,” they conclude.
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