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

Overview

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 Blood sample for genetic analysis
  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
• Other Blood sample for immunological response assessments
  Identifying specific immunological factors in patients with rare pediatric autoimmune and auto inflammatory diseases
• Other Blood sample to identify relevant biomarker of the disease
  Research biomarkers for diagnosis, prognosis and monitoring of disease activity

Primary outcome measures

• To Identify germline and somatic mutations responsible for rare autoimmune diseases or auto-inflammatory pathologies (pediatric or syndromic or familial) that began in childhood [Time frame: Baseline]

Secondary outcome measures (6)

• Measurement of disease activity according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) [Time frame: Baseline]
• Levels of anti-double stranded DNA [Time frame: Baseline]
• Levels of complement components C3 and C4 [Time frame: Baseline]
• Level of IFN Signature score [Time frame: Baseline]
• Concentration of circulating IFN-alpha [Time frame: Baseline]
• Presence or absence of anti-type I interferons autoantibodies [Time frame: Baseline]

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

France · 13 centers

• Service de rhumatologie pédiatrique Hôpital Femme-Mère-enfant — Bron
• Hôpital Jeanne de Flandre (CHU de Lille) — Lille
• Hôpital Claude Huriez (CHU de Lille) — Lille
• Hôpital Archet 2 — Nice
• Hôpital Necker-Enfants Malades (AP-HP) — Paris
• Hôpital Robert Debré (AP-HP) — Paris
• Hôpital Kremlin-Bicêtre (AP-HP) — Paris
• Hôpital Nord (CHU ST-Etienne) — Saint-Etienne
• … and 5 more centers

Identifiers

NCT: NCT06435468 · 69HCL23_1252

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗