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Pathophysiologic implications of elevated prevalence of hereditary alpha-tryptasemia in all mastocytosis subtypes

2023; Elsevier BV; Volume: 153; Issue: 1 Linguagem: Inglês

10.1016/j.jaci.2023.08.015

1097-6825

Laura Polivka, Marine Madrange, C. Bulaï Livideanu, Stéphane Barete, Thomas Ballul, Antoine Neuraz, Céline Greco, Julie Agopian, Fabienne Brenet, Patrice Dubreuil, Charles Burdet, Richard Lemal, Olivier Tournilhac, Louis Terriou, David Launay, Laurence Bouillet, C. Gourguechon, Ghandi Damaj, Laurent Frenzel, C. Méni, Hassiba Bouktit, Anne Florence Collange, C. Gaudy‐Marqueste, Marie Gousseff, Edwige Le Mouel, M. Hamidou, A. Néel, Dana Ranta, R. Jaussaud, Philippe Guilpain, Danielle Canioni, Thierry Jo Molina, Julie Bruneau, Ludovic Lhermitte, Nicolas Garcelon, Rose‐Marie Javier, F. Pelletier, Florence Castelain, F. Rétornaz, Quentin Cabrera, Patricia Zunic, Marie Pierre Gourin, E. Wierzbicka-Hainaut, Jean‐François Viallard, Christian Lavigne, C. Hoarau, I. Durieu, Maël Heiblig, Sophie Dimicoli‐Salazar, José Miguel Torregrosa-Diaz, A. Soria, Michel Arock, Olivier Lortholary, Christine Bodemer, Olivier Hermine, Julien Rossignol,

Asthma and respiratory diseases

BackgroundMastocytosis and monoclonal mast cell (MC) activation syndrome (MMAS) are heterogeneous conditions characterized by the accumulation of atypical MCs. Despite the recurrent involvement of KIT mutations, the pathophysiologic origin of mastocytosis and MMAS is unclear. Although hereditary α-tryptasemia (HαT, related to TPSAB1 gene duplication) is abnormally frequent in these diseases, it is not known whether the association is coincidental or causal.ObjectiveWe evaluated the prevalence of HαT in all mastocytosis subtypes and MMAS and assessed the pathophysiologic association with HαT.MethodsClinical data, laboratory data, KIT mutations, TPSAB1 duplication (assessed by droplet digital PCR), and HαT prevalence were retrospectively recorded for all patients with mastocytosis and MMAS registered in the French national referral center database and compared to a control cohort. To increase the power of our analysis for advanced systemic mastocytosis (advSM), we pooled our cohort with literature cases.ResultsWe included 583 patients (27 with MMAS and 556 with mastocytosis). The prevalence of HαT in mastocytosis was 12.6%, significantly higher than in the general population (5.7%, P = .002) and lower than in MMAS (33.3%, P = .02). HαT+ patients were more likely to have anaphylactic reactions and less likely to have cutaneous lesions than HαT− patients (43.0% vs 24.4%, P = .006; 57.7% vs 75.6%, respectively, P = .006). In the pooled analysis, the prevalence of HαT was higher in advSM (11.5%) than in control cohorts (5.2%, P = .01).ConclusionHere we confirm the increase incidence of anaphylaxis in HαT+ mastocytosis patients. The increased prevalence of HαT in all subtypes of systemic mastocytosis (including advSM) is suggestive of pathophysiologic involvement. Mastocytosis and monoclonal mast cell (MC) activation syndrome (MMAS) are heterogeneous conditions characterized by the accumulation of atypical MCs. Despite the recurrent involvement of KIT mutations, the pathophysiologic origin of mastocytosis and MMAS is unclear. Although hereditary α-tryptasemia (HαT, related to TPSAB1 gene duplication) is abnormally frequent in these diseases, it is not known whether the association is coincidental or causal. We evaluated the prevalence of HαT in all mastocytosis subtypes and MMAS and assessed the pathophysiologic association with HαT. Clinical data, laboratory data, KIT mutations, TPSAB1 duplication (assessed by droplet digital PCR), and HαT prevalence were retrospectively recorded for all patients with mastocytosis and MMAS registered in the French national referral center database and compared to a control cohort. To increase the power of our analysis for advanced systemic mastocytosis (advSM), we pooled our cohort with literature cases. We included 583 patients (27 with MMAS and 556 with mastocytosis). The prevalence of HαT in mastocytosis was 12.6%, significantly higher than in the general population (5.7%, P = .002) and lower than in MMAS (33.3%, P = .02). HαT+ patients were more likely to have anaphylactic reactions and less likely to have cutaneous lesions than HαT− patients (43.0% vs 24.4%, P = .006; 57.7% vs 75.6%, respectively, P = .006). In the pooled analysis, the prevalence of HαT was higher in advSM (11.5%) than in control cohorts (5.2%, P = .01). Here we confirm the increase incidence of anaphylaxis in HαT+ mastocytosis patients. The increased prevalence of HαT in all subtypes of systemic mastocytosis (including advSM) is suggestive of pathophysiologic involvement.