Biochemical characterisation and substrate-specific proteolytic diversity of venom metalloproteinases in African puff adders

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  By 4028mdk09 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11200575 Biochemical characterisation and substrate-specific proteolytic diversity of venom metalloproteinases in African puff adders Abstract The puff adder ( Bitis arietans ) is a highly venomous viper responsible for many snakebite fatalities in Africa, yet there have been few geographically comprehensive analyses of its venom proteins, particularly of the proteases that play a key role in pathology of envenoming. To address this, we have isolated, identified and characterised the bioactivity of the venom metalloproteases of puff adders obtained from a range of localities. Prominent in all venoms was a PI snake venom metalloproteinase (SVMP), derived from a larger PII precursor. This protein existed as either non-glycosylated (21 kDa) or glycosylated, the latter containing either one (26 kDa) or two N-glycans (30 kDa). All the venoms we tested contained either one or the other form: none had...

Successful venom immunotherapy with avapritinib in a patient with systemic mastocytosis

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Successful venom immunotherapy with avapritinib in a patient with systemic mastocytosis

Systemic mastocytosis (SM) is a clonal mast cell (MC) disorder characterized by tissue infiltration of MCs driving clinical symptoms.1 The disorder is characterized by activating mutations in the KIT protein, classically KIT p.D816V. SM is treated in a symptom-guided manner with therapies targeted toward bioactive MC mediators. However, the recent discoveries of targeted tyrosine kinase inhibitors have changed the treatment paradigm of indolent SM (ISM).2 Tyrosine kinase inhibitors have demonstrated to reduce MC burden and improve quality of life. To date, they have not been used to facilitate venom immunotherapy (VIT). Patients with mastocytosis and Hymenoptera venom allergy may have recurrent anaphylaxis during VIT, and adjunctive therapies are a significant unmet need to protect this patient population. Although omalizumab has been found to be effective in a subset of patients, non-IgE-mediated mechanisms may be activated by Hymenoptera venom and an increased mutated MC burden may contribute to life-threatening symptoms. We report, here, the first case of successful VIT in a patient with ISM treated with avapritinib.

Depina, L., Karmarkar, S. N., Moeller, S., Lazarovich, M., De Magalhães, A. R., Castells, M., & Giannetti, M. P. (2025). Successful venom immunotherapy with avapritinib in a patient with systemic mastocytosis. Annals of Allergy, Asthma & Immunology, 135(3), 343-344. https://doi.org/10.1016/j.anai.2025.06.015