An interventional study of biological samples in Systememic Lupus Erythematosus, Systemic Sclerosis (SSc) and Inflammatory Myopathies, sponsored by Hospices Civils de Lyon. Not yet recruiting at 3 sites in France. Open to participants aged 6 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-24.
Sponsored by Hospices Civils de Lyon · Not applicable, Interventional, and Basic science
Systemic autoimmune diseases associated with type I interferon (IFN-I) dysregulation, such as systemic lupus erythematosus, systemic sclerosis, myositis, and mixed or undifferentiated connective tissue diseases, and genetic type 1 interferonopathies are characterized by chronic and excession IFN-I signaling and production contributing to disease pathogenesis. Aberrant IFN-I production can be triggered through the activation of multiple signaling pathways, particularly those involving intracellular and extracellular RNA and DNA sensing receptors.
We hypothesize that excessive IFN-I production results from an increased tonic activation state of nucleic acid sensors and/or an enhanced responsiveness of these sensors to endogenous nucleic acids, thereby sustaining pathological IFN-I signaling and chronic inflammation.
The aim of this study is to characterize the type I interferon (IFN-I) response, defined by both the IFN-I gene signature and plasma IFN-α levels, following stimulation with a panel of ligands specific for DNA- and RNA-sensing pathways.
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.
Patient
Patient with a confirmed diagnosis of
Healthy Volunteer Participants
Exclusion Criteria:
Patient
Healthy Volunteer Participants
Patients with systemic lupus erythematosus, systemic sclerosis, myositis, and mixed or undifferentiated connective tissue diseases, and genetic type 1 interferonopathies
Biological: biological samples
Healthy volunteer
Biological: biological samples
Healthy volunteers will undergo a blood draw of a total volume of 20 mL for the following analyses: ex vivo analysis of the interferon signaling pathway (12 mL) and biological sample collection, if the patient/holder of parental authority provides consent (8 mL).
IFN-I signature score
The interferon signature assessed by transcriptomic analysis and IFN-α concentrations measured using the Simoa assay will be compared across the different disease groups and with healthy volunteers.
Time frame: Day 1 and Month 12 (if applicable)
Clinical phenotype
Correlation between the extent of specific organ involvement and the activation of nucleic acid-sensing pathways, assessed by the levels of IFN-α production.
Time frame: Day 1 and Month 12 (if applicable)
plasma IFN-α concentration
In vitro change in the IFN signature and IFN-α production in patients' PBMCs after exposure to selective inhibitors of overactivated IFN-I signaling pathways
Time frame: Day 1 and Month 12 (if applicable)
Plan to share: No
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This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Hospices Civils de Lyon