A new study published in the Journal of Allergy and Clinical Immunology suggests that long-standing reference limits for serum tryptase — a key biomarker in the diagnosis of systemic mastocytosis (SM) — may need to be updated to better reflect differences related to age and sex.
Serum tryptase is central to mastocytosis evaluation, serving as a minor diagnostic criterion for SM and an important indicator of mast cell burden. For decades, laboratories have relied on a single upper reference limit, commonly 11.4 µg/L, to define elevated baseline tryptase. But researchers say this fixed cutoff may not accurately represent normal variation across the population.
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The researchers analyzed large amounts of real-world laboratory data using a statistical approach known as an indirect method. Rather than relying on comparing data to “healthy volunteers,” this approach allowed researchers to estimate typical tryptase ranges across the population and see how those ranges change with age and sex.
The study found that the upper end of normal tryptase levels increases with age. In practical terms, this means that older adults may naturally have higher baseline tryptase levels than younger people, even without having SM. Differences between men and women were smaller, but still present, particularly later in life.
The authors stress that their findings do not change the diagnostic criteria for systemic mastocytosis. Rather, they suggest that age-adjusted reference ranges could help doctors interpret borderline tryptase results more accurately and in context.
“Our findings highlight patient age as an important variable and suggest that a universal RI cutoff (eg, 11.4 ng/mL) may miss significantly elevated tryptase concentrations in women and younger patients and overcall tryptase level elevations in elderly or male patients,” the researchers wrote. “Implementing age-and/or sex-stratified reference ranges could improve the sensitivity and specificity of tryptase screening across all patient populations and avoid unnecessary and potentially invasive follow-up testing.”
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