Investigation of Type I Interferon Excess in Patients With Systemic Autoimmune Diseases and Genetic Type I Interferonopathies

The investigators hypothesize that chronic overproduction of type I interferons (IFN-I) is driven by increased basal activation of nucleic acid-sensing pathways and/or heightened cellular responsiveness to endogenous nucleic acids, leading to sustained IFN-I signaling and persistent inflammation. The objective of the study is to characterize the IFN-I response by assessing both the interferon gene signature and plasma IFN-α levels following stimulation of PBMCs with a panel of DNA- and RNA-sensing pathway-specific ligands.

The SAFRAN study protocol comprises two study visits for patients: a mandatory Visit 1 (V1) and an optional Visit 2 (V2), the performance of which depends on the results obtained at V1. Healthy control participants will undergo Visit 1 (V1) only.

During Visit 1 (V1), the investigator will perform a clinical assessment as part of routine disease management. Disease activity will be evaluated using validated clinical scoring systems. For patients with systemic lupus erythematosus (SLE), disease activity will be assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). For patients with systemic sclerosis, skin involvement will be evaluated using the modified Rodnan Skin Score (mRSS). In addition, disease activity will be assessed in all patients using the Physician Global Assessment (PGA) scale.

During Visit 2 (V2), patients in whom an abnormality in interferon signaling is identified through the in vitro assays will undergo additional blood sampling during a routine follow-up visit conducted as part of standard clinical care. An additional blood volume of 12 mL will be collected to further characterize the abnormality detected in the previous sample (V1), within 12 months of the initial assessment.

Inclusion criteria

Patient

• Patient followed at the Hospices Civils de Lyon (HCL) for their disease.
• Patient aged over 6 years and under 60 years.
• Body weight ≥ 25 kg.
• Patient with a confirmed diagnosis of

• Systemic lupus erythematosus
• Myositis, histologically confirmed or not
• Systemic sclerosis,
• Mixed connective tissue disease, according to the Sharp or Kasukawa criteria Undifferentiated connective tissue disease, according to the criteria proposed by Mosca et al.
• Genetically confirmed monogenic lupus or monogenic interferonopathy.
• Patient, parents, or legal guardians informed about the study and having signed the informed consent form.

Healthy Volunteer Participants

• Subjects aged over 6 years and under 60 years.
• Body weight greater than or equal to 25 kg.
• Participants, parents, or legal guardians who have been informed about the study and have provided written informed consent.

Exclusion criteria

Patient

• documented infection or symptoms consistent with a bacterial or viral infection within 2 weeks prior to sampling
• Subjects currently participating in an interventional drug study
• Vaccination within 1 month prior to sampling
• Pregnant, parturient, or breastfeeding women
• Individuals deprived of liberty by judicial or administrative decision
• Individuals receiving psychiatric care
• Individuals admitted to a healthcare or social care institution for reasons other than participation in the research
• Adults subject to a legal protection measure
• Individuals not affiliated with a social security scheme or not covered by an equivalent health insurance system

Healthy Volunteer Participants

• Documented infection or symptoms consistent with a bacterial or viral infection occurring within 2 weeks prior to sample collection.
• Participant with a long-term chronic disease (ALD) or any chronic medical condition.
• Participant with a primary immunodeficiency.
• Vaccination within 1 month prior to sample collection.
• History of neoplasia (< 5 years) or ongoing neoplastic disease.
• Pregnant, parturient, or breastfeeding women.
• Individuals deprived of liberty by a judicial or administrative decision.
• Individuals receiving psychiatric care.
• Individuals admitted to a health or social care institution for purposes other than participation in research.
• Adults subject to a legal protection measure (guardianship or curatorship).
• Individuals not affiliated with a social security system or not benefiting from an equivalent health insurance scheme.