Biocollection of Rare Pediatric-onset of Autoimmune and Autoinflammatory Diseases

Autoimmune Diseases Clinical Trial

— GENIALII  

Official title:

Biocollection for the Study of Genetic and Immunological Abnormalities in Rare Pediatric-onset Autoimmune and Auto Inflammatory Diseases

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06435468
• Other study ID #: 69HCL23_1252
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 2024
• Est. completion date: July 2034

Study information

• Verified date: May 2024
• Source: Hospices Civils de Lyon
• Contact: BELOT Alexandre, Pr
• Phone: + 33 4 27 85 61 26
• Email: Alexandre.belot[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: July 2034
• Est. primary completion date: July 2034
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year and older

Eligibility

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)

Related Conditions & MeSH terms

• Autoimmune Diseases
• Autoinflammatory Disease
• Genetic Disease
• Genetic Diseases, Inborn
• Systemic Lupus

Intervention

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
• Blood sample to identify relevant biomarker of the disease
Research biomarkers for diagnosis, prognosis and monitoring of disease activity

Locations

Country	Name	City	State
France	Service de rhumatologie pédiatrique Hôpital Femme-Mère-enfant	Bron
France	Hôpital Couple Enfant	Grenoble
France	Hôpital Claude Huriez (CHU de Lille)	Lille
France	Hôpital Jeanne de Flandre (CHU de Lille)	Lille
France	Hôpital Archet 2	Nice
France	Hôpital Kremlin-Bicêtre (AP-HP)	Paris
France	Hôpital Necker-Enfants Malades (AP-HP)	Paris
France	Hôpital Robert Debré (AP-HP)	Paris
France	CLCC Henri Becquerel	Rouen
France	Hôpital Nord (CHU ST-Etienne)	Saint-Étienne	Saint Etienne

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To Identify germline and somatic mutations responsible for rare autoimmune diseases or auto-inflammatory pathologies (pediatric or syndromic or familial) that began in childhood	Identification of germline or somatic genetic mutations, based on high-throughput sequencing data (exome, genome or transcriptome).	Baseline
Secondary	Measurement of disease activity according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)	score (Min value: 0 - Max value: 105), with higher values mean higher disease activity	Baseline
Secondary	Levels of anti-double stranded DNA	in patients sera	Baseline
Secondary	Levels of complement components C3 and C4	in patients sera	Baseline
Secondary	Level of IFN Signature score	Mesured by 6-gene Type 1 IFN Signature Score	Baseline
Secondary	Concentration of circulating IFN-alpha	In serum using single-molecule array digital ELISA technology (Simoa)	Baseline
Secondary	Presence or absence of anti-type I interferons autoantibodies	in patients sera	Baseline