Patients with hereditary alpha-tryptasemia (HαT), a genetic trait frequently found in systemic mastocytosis, have an increased risk of anaphylaxis, according to a study published in The Journal of Allergy & Clinical Immunology. 

HαT is a genetic trait that has only recently been described. It appears to affect around 5% of the general population; patients with this condition have elevated tryptase levels (>8 ng/mL). 

The authors of the study sought to better characterize this condition. They accessed the French National Referral Center for Mast Cell Disorders and identified 1342 patients with mastocytosis or monoclonal mast cell activation syndrome (MMAS) who were registered between August 1, 2003, and December 31, 2022. A total of 799 patients were excluded because frozen total blood samples were unavailable, leaving 583 patients to be included in this analysis. Among these 583 patients, 556 had mastocytosis and 27 had MMAS. 

The researchers found that the prevalence of HαT was higher among patients with mastocytosis compared with the French general population (5.7%; P =.002). They also discovered that the incidence of anaphylactic reactions was higher among patients with this genetic trait compared with those without (43% vs 24.4%; P =.006). Patients with HαT were also more likely to have higher mean basal serum tryptase levels (90.6 vs 58.1 ng/mL; P =.004) and were less likely to have specific cutaneous involvement of mastocytosis (57.7% vs 75.6%; P =.006) compared with patients without HαT. 

Read more about systemic mastocytosis etiology 

The research team then turned their attention to investigate the putative involvement of HαT in the occurrence of mastocytosis. Looking specifically at cases of advanced systemic mastocytosis (ASM), the researchers found that the prevalence of HαT among patients with ASM was significantly higher than in healthy controls (11.5% vs 5.2%, P =.001). 

“Our study has investigated the largest cohort of patients with mastocytosis and MMAS and confirmed previous reports regarding elevated HαT prevalence and its association with anaphylaxis and tryptase level,” the authors wrote. “In conclusion, the prevalence of HαT is elevated in all subtypes of SM, including ASM.” 


Polivka L, Madrange M, Bulai-Livideanu C, et al. An elevated prevalence of hereditary alpha-tryptasemia in all mastocytosis subtypes: pathophysiological implicationsJ Allergy Clin Immunol. Published online August 24, 2023. doi:10.1016/j.jaci.2023.08.015