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

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

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.