New research revealed a group of proteins in the blood that behave similarly to tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. in patients with indolent systemic mastocytosis (SM), offering hope for improved diagnosis and treatment monitoring, according to research presented recently at the annual Allergy and Clinical Immunology meeting.
Tryptase, a protein released by mast cells, is often used as a measurable indicator of indolent SMIndolent SM A subtype of nonadvanced SM caused by the abnormal accumulation of mast cells in the bone marrow and other organs. Indolent SM accounts for around 90% of SM cases., but around 30% of patients do not meet the level that indicates disease (20 ng/mL), and its levels do not always reflect how patients feel. This has led scientists to look for other proteins that could serve as more reliable indicators.
“Comprehensive plasma proteome profiling in a large cohort of clinically annotated patients with ISM [indolent SM] identified several proteins with similar expression patterns to tryptase,” explained the authors of this research. “While more investigation is needed to determine correlations with symptoms and disease severity, these analyses could aid future understanding of the disease and therapeutic targets for treatment.”
Using a high-throughput technique called plasma proteome profiling, researchers examined blood samples from 156 patients enrolled in PIONEER (NCT03731260), a placebo-controlled clinical trial of avapritinib, a drug used to treat indolent SM. These samples were analyzed for 363 inflammatory proteins using the Olink Explore 384 Inflammation panel. Of these patients, 147 had paired samples taken at the start and again after 24 weeks of treatment.
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Several proteins showed strong correlations with levels of tryptase at baseline. MILR1, a receptor protein, had the strongest correlation, followed by CCL23, CD48, SIGLEC10, IL5RA, CD4, and IL13. Changes in the levels of MILR1, CCL23, CD48, and SIGLEC10 over time also matched changes in serum tryptase in patients treated with avapritinib. These patterns were not seen in patients given a placebo.
These results suggest that these proteins could be used to track progression of indolent SM or response to treatment, even in patients whose levels of tryptase do not follow expected trends. Identifying multiple proteins linked to disease activity offers a more detailed view of the condition and opens the door to discovering new drug targets.
While further study is needed to understand how these proteins connect to symptoms and severity of disease, this research brings scientists one step closer to more personalized care for people living with indolent SM. It may also help physicians better monitor the disease in patients whose levels of tryptase alone are not enough.
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