Clinical trial NCT06270524: Study of the C5a/C5aR1 Axis in IgG4-associated Disease: a Potential Therapeutic Target
Official title: Pilot Study of the C5a/C5aR1 Axis in IgG4-associated Disease: a Potential Therapeutic Target. C5-MAG4 Study.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Immunoglobulin G4-Related Disease
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2024-02-21
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed 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

Eligibility 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.

Primary outcomes:
measure: Serum C5a concentration
timeFrame: 24 months
Secondary outcomes:
measure: frequency of C5aR1+ monocytes among total monocytes
timeFrame: 24 months
measure: frequency of Tumor Growth Factor B+ (TGF-B+) monocytes among total monocytes
timeFrame: 24 months
Other outcomes:
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