Discovering new clinical biomarkers in mast cell disorders
Research type
Research Study
Full title
Discovering new clinical biomarkers linking mastocytosis (ISM), mast cell activation (MCAS) and hereditary alpha tryptasemia (HαT)
IRAS ID
347354
Contact name
Ciaren Graham
Contact email
Sponsor organisation
Queen's University Belfast
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Mast cell associated disorders represent a heterogeneous clinical group of conditions that includes systemic mastocytosis (SM), mast cell activation syndrome (MCAS) and hereditary alpha tryptasemia (HαT). Systemic mastocytosis (SM) is a rare lifelong debilitating haematological disorder that is characterised by the accumulation of neoplastic mast cells in one or several organs. SM can be divided into a range of sub-types from indolent SM (ISM), the predominant form, through to aggressive variants that can progress to mast cell leukaemia. Greater than 95% of patients with SM harbour a somatic activating mutation in the KIT gene primarily the KIT D816V mutation. Hereditary alpha tryptasemia (HαT) is a relatively common disorder that results from increased copy number of the α-tryptase gene, TPSAB1. HαT is frequently detected in SM patients and may be a novel marker for patients of increased risk of anaphylaxis. Patients with MCAS will present periodically with symptoms of systemic anaphylaxis as a result of secreted mast cell mediators. To date no trigger or genetic marker has been identified for MCAS and patients tend to be diagnosed with this disorder once all other appropriate conditions have been ruled out. The plasma proteome is a unique biomatrix that accurately reflects disease pathology. We propose to use the application of mass spectrometry proteomics to generate functional protein maps that can characterise the molecular profile that can discriminate between systemic mastocytosis (SM), mast cell activation syndrome (MCAS) and hereditary alpha tryptasemia (HαT) MCAS endotypes.
REC name
West Midlands - Black Country Research Ethics Committee
REC reference
25/WM/0148
Date of REC Opinion
13 Aug 2025
REC opinion
Further Information Favourable Opinion