According to a recently published abstract in the Journal of Allergy and Clinical Immunology, patients with anaphylaxis or suspected systemic mast cell activation who have low circulating KIT D816V but match other diagnostic markers should receive testing for clonal mast cell diseases (cMCDs) such as systemic mastocytosis (SM).
The KIT D816V mutation is present in over 90% of patients with SM and is the key driver for clonal mast cell proliferation. According to World Health Organization (WHO) guidelines, KIT D816V detection constitutes one of the main criteria for making an SM diagnosis; therefore, its absence can represent a significant diagnostic challenge.
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The authors aimed to perform a post hoc analysis of the PROSPECTOR study. A post hoc analysis is a secondary analysis that uses the data of a clinical trial or study to explore an additional hypothesis.
The PROSPECTOR study, which included over 300 patients, demonstrated that patients with suspected mast cell activation and/or an episode of anaphylaxis had higher blood levels of KIT D816V than the general population. In this secondary analysis, researchers focused on patients with a discordant expression of the gene that codes tryptase, TPSAB1. Patients with a discordant TPSAB1 have duplications or triplications of the gene without the corresponding tryptase elevation or vice versa.
Of the 27 patients with a discordant TPSAB1, 75% had serum tryptase below pathological levels (20 ng/mL), and 70% were negative for the KIT D816V mutation in a peripheral blood test. Despite the initial negative tests, 20 patients were eventually diagnosed with mCMD.
The authors remarked that patients with anaphylaxis or suspicion of mCMD and negative KIT D816V with a tryptase level above 11 ng/mL should undergo bone marrow testing to rule out SM or other forms of mCMD.
“This PROSPECTOR study follow-up analysis suggests that patients with anaphylaxis or suspected SMCA who initially screen negative on PB KIT D816V, have a BST >11.4 ng/mL, and have no HaT may warrant a full assessment for cMCD via BM biopsy,” the authors concluded.
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