Study of the C5a/C5aR1 Axis in IgG4-associated Disease: a Potential Therapeutic Target (C5-MAG4)

Public Assistance-Hospitals of Marseille (AP-HM)

Status: Begins enrollment in 1 month

Conditions: Immunoglobulin G4-Related Disease

Treatments: Procedure: Blood sampling

Study type: Interventional

Funder types: Other

Identifiers

NCT06270524

RCAPHM21_0433

Details and patient eligibility

About

This is a monocentric, comparative, cross-sectional, case-control study seeking to identify abnormalities of the C5a-C5aR1 axis between a population of patients with active IgG4-associated disease (MAG4) and two control groups: healthy subjects without MAG4 and patients with MAG4 in remission.

Full description

IgG4-associated disease is a rare fibrosing and inflammatory disorder whose pathophysiology remains poorly understood. Activation of certain monocyte/macrophage populations (in particular M2-type macrophages) has been shown to be involved during the course of the disease. The mechanisms behind this monocyte/macrophage activation are not known. Expression of the C5aR receptor on the surface of these populations, and preliminary findings of elevated C5a in these patients, suggest a potential role for this C5a-C5aR axis. Demonstration of the involvement of this pathway would open a path to therapeutic perspetives (C5aR inhibitors) for these patients, who frequently suffer from cortico-dependence and relapses. The aim of this research is to use healthcare technologies to identify cellular and molecular therapeutic targets in the context of the IgG4-associated disease

Enrollment: 66 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for patients suffering from IG4-related disease and patients in remission :

• age > 18
• diagnosis of IgG4-associated disease according to ACR/EULAR 2019 classification criteria (4,5) with a score ≥20.
• disease activity score (IgG4-RD Responder Index) ≥2 in at least one affected organ

Exclusion Criteria for patients suffering from IG4-related disease and patients in remission :

• presence of a differential diagnosis ("IgG4-RD mimicker") or exclusion criterion according to ACR/EULAR 2019 classification criteria (4,5).
• systemic corticosteroid treatment ≥5 mg/day ongoing or < 1 month ; Study C5-MAG4_RCAPHM21_0433 Protocol Version 1.1 of 16/01/2024 Page 15 of 41
• immunosuppressive therapy ongoing or < 3 months ;
• current biotherapy treatment or < 6 months;
• absence of signed informed consent;
• absence of affiliation to a Social Security scheme.
• patient participating in an ongoing therapeutic trial ;
• any condition which, in the opinion of the investigator, could influence the results of the study.

Inclusion criteria for healthy volunteers :

• age > 18

Exclusion criteria for healthy volunteers :

• infectious episode (temperature >38°C, flu-like signs) in the 30 days prior to inclusion;
• known inflammatory (including IG4-related disease) or autoimmune pathology;
• treatment with corticosteroids in progress or taken in the month prior to sampling, or immunosuppressants in progress or taken in the 3 months prior to sampling, or biotherapy in the 6 months prior to sampling;
• absence of signed informed consent;
• absence of affiliation to a Social Security scheme;
• persons taking part in an ongoing therapeutic trial;
• any condition which, in the opinion of the investigator, could influence the results of the study.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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66 participants in 3 patient groups

IgG4-RD patient

Experimental group

Description:

Patients suffering from Immunoglobulin G4-related disease (IgG4-RD).

Treatment:

Procedure: Blood sampling

patient in remission

Experimental group

Description:

Patients suffering from Immunoglobulin G4-related disease (IgG4-RD) but in remission.

Treatment:

Procedure: Blood sampling

healthy volunteers

Other group

Treatment:

Procedure: Blood sampling