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

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.

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.