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.
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
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
Parallel
biological samples
Biological/VaccineHealthy 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.
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.
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
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