Systemic Lupus, Autoimmune Diseases, Autoinflammatory Disease, Genetic Disease
Conditions
Keywords
Systemic Lupus, Genetic, rare autoimmune disease, rare autoinflammatory diseases, Pediatric-onset disease
Brief summary
Rare diseases are defined as those that affect one person in 2,000, or around three million people in France. The majority of rare diseases are caused by genetics and tend to be severe when they begin in childhood. Autoimmune and autoinflammatory diseases, such as systemic lupus, juvenile dermatomyositis, and juvenile idiopathic arthritis, are examples of rare pediatric diseases. While autoimmune diseases are characterized by an inappropriate adaptive immune response, autoinflammatory diseases involve an excess of the innate immune response. The precise mechanisms of these diseases are not yet fully understood, but recent research has led to advances in their diagnosis and identification, particularly in early onset and familial forms. However, the rarity of these diseases and limited availability of biological samples pose significant challenges. This study aims to create a biological collection, which includes primary cells (PBMC), DNA, RNA, lymphoblastic lines, and serum, that will help identify genetic and immunological abnormalities in rare autoimmune and autoinflammatory diseases through various research projects.
Detailed description
A disease is said to be rare when it affects one person in 2,000, which represents three million people in France. Most rare diseases (80%) are genetic in origin ; the earlier they start in childhood, the more severe they can be. Rare pediatric diseases include autoimmune diseases (systemic lupus, juvenile dermatomyositis and juvenile idiopathic arthritis) and autoimmune diseases (interferonopathies, FMF, CAPS, TRAPS, and DADA2). Systemic autoimmune diseases are characterized by an inappropriate adaptive immune response (mediated by autoreactive T and/or B lymphocytes) with the production of autoantibodies directed against the constituents of the self (tolerance breakdown). Autoinflammatory diseases, unlike autoimmune diseases, correspond to an excess in the innate immune response (cytokines, macrophages, NK cells, granulocytes, etc.)..The precise pathophysiological mechanisms of these diseases have yet to be fully elucidated. Recent research has led to advances in the diagnosis and identification of monogenic forms of these diseases, particularly in early onset, familial, and syndromic forms. Nevertheless, the rarity of these diseases and limited availability of biological samples are major challenges that need to be overcome. Thus, the aims of this study were as follows: \- The creation of a biological collection: primary cells (PBMC), DNA, RNA, lymphoblastic lines, and serum, which, through various research projects, will help identify genetic and immunological abnormalities in rare autoimmune and autoinflammatory diseases.
Interventions
genetic analysis (WES, WGS) for the identification of germline and somatic mutations responsible for rare autoimmune diseases or auto-inflammatory pathologies (pediatric or syndromic or familial) that began in childhood
OTHERBlood sample for immunological response assessments
Identifying specific immunological factors in patients with rare pediatric autoimmune and auto inflammatory diseases
OTHERBlood sample to identify relevant biomarker of the disease
Research biomarkers for diagnosis, prognosis and monitoring of disease activity
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
prospective, multicenter, national study
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Patients * minor or adult patient of any age with a rare dysimmune disease characterized by autoimmunity or auto-inflammation or early lymphoproliferation, having started in childhood (\<18 years), or syndromic or familial * relative of a minor or adult patient with a rare dysimmune disease characterized by autoimmunity or auto-inflammation or early lymphoproliferation, having started in childhood (\<18 years of age) or syndromic or familial, * weight greater than 5 kg * Patient/parents/guardians who were informed of the study and signed the consent form. * patient affiliated to a social security scheme Healthy volunteer participants * minor or adult participants with no age restrictions * weight over 5 kg * Subject /Parents/guardians who were informed of the study and signed a consent form. * Patient affiliated to a social security scheme
Exclusion criteria
Patients \- Subjects /Parents/guardians, refusing to participate in the study Healthy volunteer participants : * active infection (viral, bacterial, parasitic) * history of neoplasia (\< 5 years) or current neoplasia * participants with a personal or family history of autoimmune disease * immunocompromised participant (immune deficiency or transplant recipient) * Subjects/parents/guardians refusing to participate in the study * Adults under legal protection (guardianship, curatorship)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Identify germline and somatic mutations responsible for rare autoimmune diseases or auto-inflammatory pathologies (pediatric or syndromic or familial) that began in childhood | Baseline | Identification of germline or somatic genetic mutations, based on high-throughput sequencing data (exome, genome or transcriptome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Levels of anti-double stranded DNA | Baseline | in patients sera |
| Levels of complement components C3 and C4 | Baseline | in patients sera |
| Measurement of disease activity according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) | Baseline | score (Min value: 0 - Max value: 105), with higher values mean higher disease activity |
| Concentration of circulating IFN-alpha | Baseline | In serum using single-molecule array digital ELISA technology (Simoa) |
| Presence or absence of anti-type I interferons autoantibodies | Baseline | in patients sera |
| Level of IFN Signature score | Baseline | Mesured by 6-gene Type 1 IFN Signature Score |
Countries
France
Contacts
Primary ContactBELOT Alexandre, Pr
Backup ContactPLASSART Samira
Outcome results
None listed