## Protocol Section
### Identification Module
**NCT ID:** NCT06435468

**Acronym:** GENIALII

**Brief Title:** 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

#### Organization Study ID Info
**ID:** 69HCL23_1252
#### Organization
**Class:** OTHER
**Full Name:** Hospices Civils de Lyon
### Status Module
#### Completion Date
**Date:** 2034-07

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-24

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2034-07

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-07
**Study First Submit QC Date:** 2024-05-24
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Hospices Civils de Lyon

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Systemic Lupus

- Autoimmune Diseases

- Autoinflammatory Disease

- Genetic Disease

**Keywords:**

- Systemic Lupus

- Genetic

- rare autoimmune disease

- rare autoinflammatory diseases

- Pediatric-onset disease

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** prospective, multicenter, national study

##### Masking Info

**Masking:** NONE

**Primary Purpose:** OTHER

#### Enrollment Info

**Count:** 400

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** minors or adults of any age with a rare dysimmune disease characterized by autoimmunity, autoinflammation or early lymphoproliferation, with onset in childhood (\<18 years), or syndromic or familial.

**Intervention Names:**

- Genetic: Blood sample for genetic analysis

- Other: Blood sample for immunological response assessments

- Other: Blood sample to identify relevant biomarker of the disease

**Label:** Patient with with a rare dysimmune disease

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** minor or adult participant without age restriction weighing more than 5 kg

**Intervention Names:**

- Other: Blood sample for immunological response assessments

- Other: Blood sample to identify relevant biomarker of the disease

**Label:** Healthy volunteer participants

**Type:** OTHER

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Patient with with a rare dysimmune disease

**Description:** 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

**Name:** Blood sample for genetic analysis

**Type:** GENETIC

#### Intervention 2

**Arm Group Labels:**

- Healthy volunteer participants

- Patient with with a rare dysimmune disease

**Description:** Identifying specific immunological factors in patients with rare pediatric autoimmune and auto inflammatory diseases

**Name:** Blood sample for immunological response assessments

**Type:** OTHER

#### Intervention 3

**Arm Group Labels:**

- Healthy volunteer participants

- Patient with with a rare dysimmune disease

**Description:** Research biomarkers for diagnosis, prognosis and monitoring of disease activity

**Name:** Blood sample to identify relevant biomarker of the disease

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Identification of germline or somatic genetic mutations, based on high-throughput sequencing data (exome, genome or transcriptome).

**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

**Time Frame:** Baseline

#### Secondary Outcomes

**Description:** score (Min value: 0 - Max value: 105), with higher values mean higher disease activity

**Measure:** Measurement of disease activity according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)

**Time Frame:** Baseline

**Description:** in patients sera

**Measure:** Levels of anti-double stranded DNA

**Time Frame:** Baseline

**Description:** in patients sera

**Measure:** Levels of complement components C3 and C4

**Time Frame:** Baseline

**Description:** Mesured by 6-gene Type 1 IFN Signature Score

**Measure:** Level of IFN Signature score

**Time Frame:** Baseline

**Description:** In serum using single-molecule array digital ELISA technology (Simoa)

**Measure:** Concentration of circulating IFN-alpha

**Time Frame:** Baseline

**Description:** in patients sera

**Measure:** Presence or absence of anti-type I interferons autoantibodies

**Time Frame:** Baseline

### Eligibility Module

**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)

**Healthy Volunteers:** True

**Minimum Age:** 1 Year

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Alexandre.belot@chu-lyon.fr

**Name:** BELOT Alexandre, Pr

**Phone:** + 33 4 27 85 61 26

**Role:** CONTACT

**Contact 2:**

**Email:** Samira.plassart@chu-lyon.fr

**Name:** PLASSART Samira

**Phone:** + 33 4 27 85 54 42

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Saint-Étienne

**Contacts:**

***Contact 1:***

- **Email:** Franck.ZEKRE@chu-st-etienne.fr

- **Name:** Franck Zekré, MD

- **Role:** CONTACT

**Country:** France

**Facility:** Hôpital Nord (CHU ST-Etienne)

**State:** Saint Etienne

**Location 2:**

**City:** Bron

**Contacts:**

***Contact 1:***

- **Name:** BELOT Alexandre, Pr

- **Role:** CONTACT

**Country:** France

**Facility:** Service de rhumatologie pédiatrique Hôpital Femme-Mère-enfant

**Zip:** 69500

**Location 3:**

**City:** Grenoble

**Contacts:**

***Contact 1:***

- **Email:** apagnier@chu-grenoble.fr

- **Name:** PAGNIER Anne, MD

- **Role:** CONTACT

**Country:** France

**Facility:** Hôpital Couple Enfant

**Zip:** 38043

**Location 4:**

**City:** Lille

**Contacts:**

***Contact 1:***

- **Email:** Heloise.REUMAUX@chu-lille.fr

- **Name:** REUMAUX Héloïse, MD

- **Role:** CONTACT

**Country:** France

**Facility:** Hôpital Jeanne de Flandre (CHU de Lille)

**Zip:** 59000

**Location 5:**

**City:** Lille

**Contacts:**

***Contact 1:***

- **Email:** eric.hachulla@chru-lille.fr

- **Name:** HACHULLA Éric, MD, PhD

- **Role:** CONTACT

**Country:** France

**Facility:** Hôpital Claude Huriez (CHU de Lille)

**Zip:** 59037

**Location 6:**

**City:** Nice

**Contacts:**

***Contact 1:***

- **Email:** de-guillebon-de-resnes.jm@chu-nice.fr

- **Name:** DE GUILLEBON DE RESNES Jean-Marie, MD

- **Role:** CONTACT

**Country:** France

**Facility:** Hôpital Archet 2

**Zip:** 06200

**Location 7:**

**City:** Paris

**Contacts:**

***Contact 1:***

- **Email:** brigitte.bader-meunier@aphp.fr

- **Name:** Bader-Meunier Brigitte, MD

- **Role:** CONTACT

**Country:** France

**Facility:** Hôpital Necker-Enfants Malades (AP-HP)

**Zip:** 75015

**Location 8:**

**City:** Paris

**Contacts:**

***Contact 1:***

- **Email:** ulrich.meinzer@aphp.fr

- **Name:** Meinzer Ulrich, MD, PhD

- **Role:** CONTACT

**Country:** France

**Facility:** Hôpital Robert Debré (AP-HP)

**Zip:** 75935 Paris

**Location 9:**

**City:** Paris

**Contacts:**

***Contact 1:***

- **Name:** Koné-Paut Isabelle, MD, PhD

- **Role:** CONTACT

**Country:** France

**Facility:** Hôpital Kremlin-Bicêtre (AP-HP)

**Zip:** 94270

**Location 10:**

**City:** Rouen

**Contacts:**

***Contact 1:***

- **Email:** fabrice.jardin@chb.unicancer.fr

- **Name:** JARDIN Fabrice, MD, PhD

- **Role:** CONTACT

**Country:** France

**Facility:** CLCC Henri Becquerel

**Zip:** 76038

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: All

- Name: All Conditions

- Abbrev: BC20

- Name: Immune System Diseases

### Condition Browse Module - Browse Leaves

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M4629

- Name: Autoimmune Diseases

- Relevance: HIGH

- As Found: Autoimmune Diseases

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: HIGH

- As Found: Genetic Diseases

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000030342

- Term: Genetic Diseases, Inborn

- ID: D000001327

- Term: Autoimmune Diseases

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
