Clinical trial NCT06435468: Biocollection of Rare Pediatric-onset of Autoimmune and Autoinflammatory Diseases
Official title: Biocollection for the Study of Genetic and Immunological Abnormalities in Rare Pediatric-onset Autoimmune and Auto Inflammatory Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Systemic Lupus
Autoimmune Diseases
Autoinflammatory Disease
Genetic Disease
Keywords: Systemic Lupus
Genetic
rare autoimmune disease
rare autoinflammatory diseases
Pediatric-onset disease
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2024-05-30
Enrollment: 400
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, multicenter, national study
Primary purpose: OTHER

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.

Eligibility criteria: 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)

Primary outcomes:
measure: To Identify germline and somatic mutations responsible for rare autoimmune diseases or auto-inflammatory pathologies (pediatric or syndromic or familial) that began in childhood
timeFrame: Baseline
Secondary outcomes:
measure: Measurement of disease activity according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)
timeFrame: Baseline
measure: Levels of anti-double stranded DNA
timeFrame: Baseline
measure: Levels of complement components C3 and C4
timeFrame: Baseline
measure: Level of IFN Signature score
timeFrame: Baseline
measure: Concentration of circulating IFN-alpha
timeFrame: Baseline
measure: Presence or absence of anti-type I interferons autoantibodies
timeFrame: Baseline
Other outcomes:
Locations:
city: Saint-Étienne
country: France
facility: Hôpital Nord (CHU ST-Etienne)
state: Saint Etienne
city: Bron
country: France
facility: Service de rhumatologie pédiatrique Hôpital Femme-Mère-enfant
city: Grenoble
country: France
facility: Hôpital Couple Enfant
city: Lille
country: France
facility: Hôpital Jeanne de Flandre (CHU de Lille)
city: Lille
country: France
facility: Hôpital Claude Huriez (CHU de Lille)
city: Nice
country: France
facility: Hôpital Archet 2
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades (AP-HP)
city: Paris
country: France
facility: Hôpital Robert Debré (AP-HP)
city: Paris
country: France
facility: Hôpital Kremlin-Bicêtre (AP-HP)
city: Rouen
country: France
facility: CLCC Henri Becquerel
Study officials:
References: