Clinical impact of the TPSAB1 genotype in mast cell diseases: A REMA study in a cohort of 959 individuals

Background A close association between hereditary alpha‐tryptasemia (HAT) and mast cell (MC) disorders has been previously reported. However, the relationship between HAT and the diagnostic subtypes and clinical features of MC disorders still remains to be established. Objective To determine the prevalence of HAT in healthy donors (HD) vs patients with different diagnostic subtypes of MC activation syndromes (MCAS) and mastocytosis, and its relationship with the clinical behavior of the disease. Methods A total of 959 subjects were studied including 346 healthy donors (HD), 464 mastocytosis, and 149 non‐clonal MCAS patients. Molecular studies to assess the TPSAB1 genotype were performed, and data on serum baseline tryptase (sBT) and basal MC‐mediator release episodes and triggers of anaphylaxis were collected. Results HAT was detected in 15/346 (4%) HD versus 43/149 (29%) non‐clonal MCAS and 84/464 (18%) mastocytosis cases. Among mastocytosis, HAT was more frequently found in patients with MC‐restricted KITD816V (21% vs. 10% among multilineage KITD816V patients; p = .008). Overall, median sBT was higher in cases presenting with HAT (28.9 vs. 24.5 ng/mL; p = .008), while no significant differences in sBT were observed among HAT+ mastocytosis patients depending on the presence of 1 vs. ≥2 extra copies of the α‐tryptase gene (44.1 vs. 35.2 ng/mL, p > .05). In turn, anaphylaxis was more frequently observed in HAT+ versus HAT− mastocytosis patients (76% vs. 65%; p = .018), while HAT+ and HAT− patients who did not refer anaphylaxis as the presenting symptom (n = 308) showed a similar prevalence of subsequent anaphylaxis (35% vs. 36%, respectively). Conclusion The frequency of HAT in MC disorders varies according to the diagnostic subtype of the disease. HAT does not imply a higher risk (and severity) of anaphylaxis in mastocytosis patients in whom anaphylaxis is not part of the presenting symptoms of the disease. This study aimed to determine the prevalence of hereditary alpha‐tryptasemia (HAT) in healthy controls and patients with different diagnostic subtypes of mast cell activation syndromes and mastocytosis. HAT was detected in 4% healthy controls and in 29% of nc‐MCAS. Among mastocytosis patients, HAT was detected in 23% CM, 22% BMM, 16% ISM, 13% SSM, and 13% AvdSM cases. Median sBT was higher in cases presenting with HAT+ compared to HAT− mastocytosis patients. However, among HAT+ patients, there is no correlation between the number of extra copies of the