Mastocytosis
Conditions
Keywords
Mastocytosis, Mast cells, Cellular heterogeneity, CD 45+, CD 34+
Brief summary
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.
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.
Interventions
GENETICscRNAseq
A blood test tube (only for scRNAseq, 2 tubes of 10 ml per patient)
PROCEDUREtwo Skin biopsies
2 skin biopsies from a lesional area
PROCEDUREone Skin biopsies
1 skin biopsies from a lesional area
Sponsors
University Hospital, Toulouse
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study of the diversity of skin CD 45+ cells and circulating blood CD 34+ cells | 24 month and one week | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study of common or differential transcripts | 24 month and one week | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| marker | 24 month and one week | through advanced imaging techniques (multiplexed imaging), marker in patients with isolated cutaneous mastocytosis and systemic mastocytosis will be identified compared with control sample |
| marker - isolated cutaneous mastocytosis | 24 month and one week | through advanced imaging techniques (multiplexed imaging), marker in patients with isolated cutaneous mastocytosis will be identified compared with control sample |
| marker - systemic mastocytosis | 24 month and one week | through advanced imaging techniques (multiplexed imaging), marker in patients with systemic mastocytosis will be identified compared with control sample |
Countries
France
Contacts
Primary ContactCristina Bulai Livideanu, MD
Outcome results
None listed