Study of Cellular Heterogeneity in Patients With Mastocytosis (MastCellHet)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Mastocytosis
• Intervention / Treatment: Genetic: scRNAseq; Procedure: two Skin biopsies; Procedure: one Skin biopsies

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cristina Bulai Livideanu, MD; Phone Number: +33 0567778138; Email: livideanu.c@chu-toulouse.fr

Study Locations

• France
  • Toulouse, France, 31059
    • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: patients with isolated cutaneous mastocytosis with associated skin involvement - RNAseq	Genetic: scRNAseq; A blood test tube (only for scRNAseq, 2 tubes of 10 ml per patient); Procedure: two Skin biopsies; 2 skin biopsies from a lesional area
Other: patients with mastocytosis indolent systemic with associated skin involvement	Procedure: one Skin biopsies; 1 skin biopsies from a lesional area
Other: patients with isolated cutaneous mastocytosis with associated skin involvement	Procedure: one Skin biopsies; 1 skin biopsies from a lesional area
Other: patients with mastocytosis indolent systemic with associated skin involvement - RNAseq	Genetic: scRNAseq; A blood test tube (only for scRNAseq, 2 tubes of 10 ml per patient); Procedure: two Skin biopsies; 2 skin biopsies from a lesional area

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study of the diversity of skin CD 45+ cells and circulating blood CD 34+ cells	This study aims to examine the diversity of CD 45+ cells in the skin and CD 34+ cells in the circulating blood in patients. The approach used will be single cell sequencing (scRNAseq) to identify the transcriptomic profiles of the different cell populations in these two types of mastocytosis.	24 month and one week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study of common or differential transcripts	This part of the study will focus on analyzing common or differential genetic transcripts between patients with isolated cutaneous mastocytosis and those with systemic mastocytosis. The aim is to understand the underlying molecular differences between these two forms of the disease.	24 month and one week

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
marker	through advanced imaging techniques (multiplexed imaging), marker in patients with isolated cutaneous mastocytosis and systemic mastocytosis will be identified compared with control sample	24 month and one week
marker - isolated cutaneous mastocytosis	through advanced imaging techniques (multiplexed imaging), marker in patients with isolated cutaneous mastocytosis will be identified compared with control sample	24 month and one week
marker - systemic mastocytosis	through advanced imaging techniques (multiplexed imaging), marker in patients with systemic mastocytosis will be identified compared with control sample	24 month and one week

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Cristina Bulai Livideanu, MD, Toulouse univiversity hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): June 8, 2026
• Study Completion (Estimated): June 15, 2026

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: May 21, 2024
• First Posted (Actual): May 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 21, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Mastocytosis; Mast cells; Cellular heterogeneity; CD 45+; CD 34+
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Mast Cell Activation Disorders; Mastocytosis
• Other Study ID Numbers: RC31/23/0362; 2024-A00021-46 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No