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Hereditary alpha tryptasemia associated with mastocytosis but not other conditions

Published online: June 22, 2021

Hereditary alpha tryptasemia (HaT) is an inherited genetic trait where an individual has one or more extra copies of the alpha tryptase gene. Tryptase is a chemical produced by immune cells called mast cells during allergic reactions and is known to be higher in patients with HaT. HaT is found in up to 8% of the general population and has been linked in earlier reports to a variety of seemingly unrelated medical conditions including flushing, itching, gastric reflux, increased joint flexibility, blood pressure changes with standing, and allergy to bee stings. However, only a few studies have been published on HaT and they have conflicting findings which raises the question of whether HaT truly increases the risk of developing these medical conditions.
The Journal of Allergy and Clinical Immunology (JACI) recently published a research article by Chollet & Akin in which individuals were tested for HaT. Patients in an allergy clinic and patients with mastocytosis were invited to participate in the study. Mastocytosis is a rare condition where the body makes too many mast cells. The study authors also recruited a group of random individuals from a DNA biorepository of 500 random donors to test for associations between HaT and medical conditions in people from the general population. Every participant completed a survey about their symptoms and medical history. They had their DNA analyzed for the number of copies of the alpha tryptase gene after completing the survey to make sure that their survey answers would not be biased by the result of their genetic test. Some participants also underwent a physical exam to objectively confirm joint flexibility and changes in blood pressure with standing and their medical charts were reviewed for allergy testing results and to look for elevations in blood and urine markers of mast cell activation.

Similar to previous research, this study identified HaT in 8% of people from the biorepository. It also found HaT in 18% of patients with mastocytosis. Unlike other studies, there was no difference in the symptoms or medical history of individuals with HαT as compared to people without HaT. Specifically, HaT was not associated with asthma, allergic rhinitis, Ehlers-Danlos syndrome (EDS), hypothyroidism, anxiety/depression, migraines, mast cell activation syndrome, postural orthostatic hypotension (POTS), gastric reflux, irritable bowel syndrome (IBS), skeletal deformity or allergy to bee stings. Individuals with HaT had similar rates of flushing, itching, chronic pain, sleep disruption, and unexplained medical symptoms as individuals without HaT. There was no difference in joint flexibility or changes in blood pressure with standing when assessed by physical exam. Individuals with HaT had a higher blood tryptase level than those without HaT, but there was no difference in urinary markers of mast cell activation.

This study indicates that there are no particular clinical features associated with HaT, except that HaT is found more frequently in patients with mastocytosis. The strengths of this study are that it included both individuals with HaT and age- and sex-matched individuals without HaT, participants were unaware of their genetic status before completing the survey to prevent bias in their answers, and that participants were recruited from different populations including the largest unselected population reported thus far. When possible, findings were confirmed by physical exam and chart review. These measures help to limit biases which may affect study results and are hypothesized by the authors to be key factors in why previous studies have had conflicting results. Ultimately, the authors concluded that HaT is a genetic variant rather than a mast cell disorder, and that while some individuals with HaT may have symptoms related to this genetic variant, these symptoms are neither consistent between individuals nor pervasive. The increased prevalence of HaT in patients with mastocytosis does, however, suggest a link between HaT and mastocytosis. Further research needs to be completed to understand the nature of this relationship and to determine whether additional clinical screening is indicated for individuals with HaT.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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