What is considered a “normal” tryptase threshold (~11 μg/L) should be maintained rather than raised, and having low levels of tryptase alone is insufficient to rule out systemic mastocytosis (SM), according to findings recently presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting.
Tryptase is an enzyme secreted by mast cells. Tryptase levels are often elevated in the blood of people with SM, so checking tryptase levels is one of the methods doctors use to help diagnose the disease. Levels greater than 20 μg/mL often point to SM.
What is a mast cell?
Mast cells are specialized cells of the immune system that mediate inflammatory responses and allergic reactions. They are found in the body’s connective tissue.
However, a condition called hereditary alpha-tryptasemia (HαT) can also cause high levels of tryptase, prompting accuracy concerns. Around 5% of the general population has HαT. Some researchers have suggested raising what is considered the “normal” tryptase level to help account for this population when checking tryptase.
Further complicating diagnosis, not everyone with SM has elevated levels of tryptase.
Read more about SM testing and diagnosis
The authors aimed to assess the adequacy of current cutoff levels for serum tryptase for diagnosing SM. They examined electronic health record (EHR) data from almost 6,500 patients with initial ambulatory tryptase measurements at Penn Medicine. The results where correlated with the presence of KIT D816V mutations, which are also commonly associated with SM.
The researchers found that a result below the current cutoff level didn’t always rule SM out: the KIT D816V mutation was found in patients across all tryptase levels. They recommended keeping the current tryptase limits, and noted trptase levels alone shouldn’t be used to rule out SM.
“Retrospective EHR data analyses support maintaining conventional tryptase upper reference limits (∼11 μg/L) rather than raising them. KIT D816V results argue against using tryptase alone to rule out SM. Larger EHR studies should help refine interpretive thresholds,” the authors concluded.
The researchers also found that trypase levels tended to be naturally higher in men, white individuals and older adults.
Sign up here to get the latest news, perspectives, and information about SM sent directly to your inbox. Registration is free and only takes a minute.
