Clinical trial NCT05292768: Are Mast Cells Involved in Autoinflammatory Diseases
Official title: Are Mast Cells Involved in Autoinflammatory Diseases
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Autoinflammatory Disease
FMF
TRAPS
MKD
Cryopyrin Associated Periodic Syndrome
Haploinsufficiency
Keywords: Autoinflammatory disease
Mast cells
Mast cell activation syndrome
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut Imagine
First posted: 2022-03-23
Enrollment: 590
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Inpatients and outpatients wil be recruited in tertiary university centres of the Assitance Publique des Hopitaux de Paris.

Healthy controls will be recruited from volunteer healthcare workers in Assitance Publique des Hopitaux de Paris

Brief summary: Autoinflammatory diseases (AID) are caused by innate immunity dysregulation. AID pathophysiology is only partly understood, especially in the case of unclassified AID. Mast cells (MC) are innate immune cells associated with a spectrum of disease between systemic mastocytosis and mast cell activation syndrome. The implication of MC has been shown in cryopyrin associated periodic syndrome (CAPS).Our aim is to evaluate the involvement of MC in AID by assessing clinical and biological signs of MC activation and studying cutaneous and digestive biopsies.

Detailed description: Autoinflammatory diseases (AID) are caused by innate immunity dysregulation and characterized by recurrent bouts of fever, frequently associated with digestive, articular or cutaneous symptoms, and sometimes ocular, auricular or neurologic inflammation. The most frequent monogenic AID is Familial Mediterranean fever (FMF).

Despite recent genetic progress AID pathophysiology is only partly understood, especially in the case of unclassified AID.

Mast cells (MC) are innate immune cells associated with a spectrum of disease between systemic mastocytosis and mast cell activation syndrome (MCAS). In MCAS, patients have various symptoms including abdominal pain, bloating, pruritus, flush, anxiety, fatigue, among which some are similar to those seen in patients with AID. The implication of MC has been shown in cryopyrin associated periodic syndrome (CAPS).

Our hypothesis is that MC could be involved in AID pathophysiology,

In order to test this hypothesis, we plan to study :

* clinical MC activation symptoms via a standardized clinical score
* biological MC mediators : by measuring total serum tryptase and histamine in total blood, plasma and urine
* MC infiltration on gastro-intestinal (GI) tract and cutaneous biopsies We will compare clinical MC activation score in AID patients to patients with mastocytosis, with other inflammatory diseases, and with healthy controls.

Eligibility criteria: Inclusion Criteria:

* Patients \>18 years old with Auto-inflammatory diseases already followed up at the CeRéMAIA (french national reference center for autoinflamamtory diseases and AA amyloidosis) of Tenon hospital and included in the JIRcohorte
* Healthy adult controls, age- and sex-matched with MAI patients, and controls with mastocytosis, an immuno-inflammatory disease.
* Subject affiliated to or entitled to a social security scheme
* Collection of the patient's or healthy control's non-opposition

Exclusion Criteria:

* Subjects unable to answer questions or express themselves
* Subjects who do not speak French
* Subject deprived of liberty or under legal protection.

Primary outcomes:
measure: : presence of MCAS
timeFrame: at inclusion
Secondary outcomes:
measure: comparison of clinical symptoms of MC activation between groups
timeFrame: at inclusion
measure: MC mediators associated to AID
timeFrame: at inclusion
measure: MC infiltration in biopsies from AID patients
timeFrame: at inclusion, retrospectively
measure: basophilic polynuclear activation in AID patients
timeFrame: at inclusion, retrospectively
Other outcomes:
Locations:
city: Paris
country: France
facility: Service de Médecine Interne
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Sophie GEORGIN-LAVIALLE, PU-PH
role: PRINCIPAL_INVESTIGATOR
References: