The evaluation of hereditary alpha-tryptasemia (HαT) status could provide valuable information and help improve the management of patients with systemic mastocytosis (SM), according to researchers from Italy.

“We speculate that the presence of HαT may facilitate the diagnosis of the disease, and contribute to findings of the diagnostic workup, with a low (or KIT-unmutated) and non-diagnostic number of MCs (mast cells) according to current diagnostic criteria,” the researchers said.

The study, published in the Journal of Allergy and Clinical Immunology, showed that HαT carriers (HαT+) had a lower mast cell-associated disease burden but higher levels of basal serum tryptase than subjects with a normal TPSAB1 copy number (HαT-). Indolent SM and advanced SM clinical variants, including SM with an associated hematological neoplasm, aggressive SM, and mast cell leukemia were more frequently diagnosed among HαT- individuals, whereas monoclonal mast cell activation syndrome and bone marrow mastocytosis were more frequently diagnosed in HαT+ patients.

The frequency of the KIT D816V mutation was higher in HαT- patients than HαT+ patients. Moreover, HαT- patients had higher degree of mast cell infiltration and more mast cell clusters, as well as a trend toward a higher grade of bone marrow fibrosis, the presence of spindle-shaped mast cells, lymphoid aggregates, eosinophilia, and dysplasia.

Read more about SM etiology

HαT+ patients had a significantly higher frequency of anaphylaxis and more mediator-related symptoms. The most common cause of anaphylaxis was hymenoptera sting. On the other hand, skin lesions were more frequently observed in HαT- patients.

The researchers also found a higher incidence of HαT+ cases among patients with SM compared with the general population, corroborating the observations from previous studies.

The study enrolled 444 patients diagnosed with SM (90.8%), monoclonal mast cell activation syndrome (4.3%), or cutaneous mastocytosis (4.9%). Of the 444 patients, 59 were HαT carriers, most presenting with the 2α (45.8%) or 2α+1α (40.7%) phenotype.

Reference

Sordi B, Vanderwert F, Crupi F, et al. Disease correlates and clinical relevance of hereditary alpha-tryptasemia in patients with systemic mastocytosis. J Allergy Clin Immunol. Published online October 26, 2022. doi:10.1016/j.jaci.2022.09.038