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Investigation of Type I Interferon Excess in Patients With Systemic Autoimmune Diseases and Genetic Type I Interferonopathies
Condition(s) studied
Systememic Lupus ErythematosusSystemic Sclerosis (SSc)Inflammatory MyopathiesConnective Tissue DiseasesType 1 Interferonopathies
Investigational drug(s) / intervention(s)
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).
Study summary
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.
Eligibility
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.
Primary outcome measure(s)
- IFN-I signature score — Day 1 and Month 12 (if applicable)
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.
Trial sites (3)
| Facility | City | Region | Status |
|---|
| Hôpital Femme-Mère-Enfant |
Bron |
France |
|
| Hôpital Edouard Herriot |
Lyon |
France |
|
| Centre Hospitalier Lyon-Sud |
Oullins |
France |
|
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