Are Mast Cells Involved in Autoinflammatory Diseases (INFLAMAST)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Autoinflammatory Disease; FMF; TRAPS; MKD; Cryopyrin Associated Periodic Syndrome; Haploinsufficiency

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.

• Study Type: Observational
• Enrollment (Anticipated): 590

Contacts and Locations

• Study Contact: Name: Sophie GEORGIN-LAVIALLE, PU-PH; Phone Number: +33 (0)1 56 01 72 04 or 60 77; Email: sophie.georgin-lavialle@aphp.fr
• Study Contact Backup: Name: Nabiha Sbeih, MD; Phone Number: +33 (0)1 84 82 74 03; Email: nabiha.sbeih@gmail.com

Study Locations

• France
  • Paris, France, 75020
    • Service de Médecine Interne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• 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

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort
Patients with AID
Control patients with mastocytosis
Control patients with normal digestive biopsy
Control patients with renal biopsy
Control patients with inflammatory disease
Healthy control from healthcare workers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
: presence of MCAS	presence of clinical and biological markers of MCAS	at inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
comparison of clinical symptoms of MC activation between groups	we will compare clinical symptoms of MC activation between AID patients and other groups	at inclusion
MC mediators associated to AID	determine which MC mediators are elevated in AID and if they correlate with inflammation	at inclusion
MC infiltration in biopsies from AID patients	we will study MC infiltration in digestive, renale and cutaneous biopsies from patients with AID and compare them with biopsies from the other groups from subgroups of patients who had a biopsy performed.	at inclusion, retrospectively
basophilic polynuclear activation in AID patients	we will study basophilic polynuclear activation from blood samples of AID patients	at inclusion, retrospectively

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut Imagine

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): October 1, 2026
• Study Completion (Anticipated): October 1, 2026

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): March 23, 2022

Study Record Updates

• Last Update Posted (Actual): March 23, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Mast cells; Autoinflammatory disease; Mast cell activation syndrome
• Additional Relevant MeSH Terms: Skin Diseases; Genetic Diseases, Inborn; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Cryopyrin-Associated Periodic Syndromes
• Other Study ID Numbers: APHP210126

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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