Study of Cellular Heterogeneity in Patients With Mastocytosis

Study of Cellular Heterogeneity in Patients With Mastocytosis (MastCellHet) Mastocytosis Cell Heterogeneity

This study will aim to study the heterogeneity of skin-resident mast cells and of blood circulating hematopoietic progenitors in patients suffering from isolated Cutaneous Mastocytosis and from systemic Mastocytosis with skin lesions.

Mastocytosis is a rare disease caused by abnormal mast cell accumulation/proliferation. Its clinical features are very heterogeneous. Among adult patients, 15% present an isolated cutaneous mastocytosis (CM), while 85% of them present a systemic mastocytosis (SM) with cutaneous lesions. In addition, regardless of the diagnosis (i.e., CM or SM), it is frequent to observe mast cell-dependent symptoms of variable severity, ranging from gastrointestinal discomfort to life-threatening reactions. To date, the origin of such heterogeneous manifestations in adult patients is still elusive. Researchers hypothesize that the heterogeneity in mastocytosis symptoms might originate, at least in part, from a broad diversity of mast cell populations in patients. This study will aim to uncover heterogeneity of skin-resident mast cells and of blood circulating hematopoietic progenitors in patients suffering from isolated CM or SM with skin lesions. Patients with isolated CM and patients with SM with cutaneous involvement will be recruited from the Mastocytosis Expert Center of Toulouse.

Cluster of Differentiation (CD) 45+ cells from skin biopsies and CD 34+ cells from blood will be isolated by magnetic cell sorting for scRNAseq. Bioinformatics analysis pipeline will be used in order to analyze the cellular heterogeneity of skin lesions and blood from CM and SM patients by comparing their transcriptomic signatures. Using trajectories analysis, the researchers will then deduce infer a differentiation pathway between blood progenitors and cutaneous mast cells at the patient level. Researchers will then confirm the expression of identified relevant biomarkers by highly multiplexed imaging in frozen skin biopsies from CM patients and from SM patients.

Inclusion Criteria:

• Criteria related to the study population:
• Subject affiliated with a social security or insurance scheme
• Subject who has given written consent to his participation in the study
• Criteria related to the studied pathology:
• Subject diagnosed with isolated cutaneous or indolent systemic mastocytosis with associated skin involvement defined according to World Health Organization criteria (and/or international criteria for cutaneous mastocytosis)
• Subjects whose KIT mutation status is known in the skin, bone marrow, and blood

Exclusion Criteria:

• Criteria related to the study population:
• Sun exposure of the biopsied areas expected within the 4 weeks preceding
• Subjects who have had exposure to sunlight or artificial UV radiation within the 2 weeks preceding inclusion at the biopsied areas
• Adult patients under legal protection, guardianship, or curatorship
• Pregnant or lactating women
• Criteria related to the studied pathology:
• Subjects with an advanced version of the pathology or advanced systemic mastocytosis (SAMA)
• Subjects with a known history of allergy or intolerance to local anesthetics
• Subjects who have previously shown abnormalities in skin healing or any other contraindication to skin biopsy
• Subjects with recognized addiction to alcoholism or drug abuse
• Subjects with a hereditary or acquired disorder of hemostasis
• Subjects with a severe or acute chronic condition judged by the investigator as incompatible with the trial
• Subjects presenting a clinically incompatible immune deficiency with the study
• Patients without a well-established diagnosis of mastocytosis
• Patients included in a therapeutic study for indolent systemic mastocytosis
• Treatment-related criteria:
• Any topical or systemic treatment for atopic dermatitis (including phototherapy) ongoing or stopped at least 14 days before the inclusion visit
• Systemic corticosteroids within the 4 weeks preceding the inclusion visit
• Ongoing systemic treatment likely to interfere with the healing process
• Subjects who have undergone physical treatment (radiotherapy, etc.) on the biopsy area in the past 6 months
• History of treatment or concomitant treatment that may interfere with the conduct of the study as determined by the investigator