TRANSIMMUNOM: Phenomics in Autoimmune and Inflammatory Diseases

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Recruiting

CT.gov ID

NCT02466217

Collaborator

National Research Agency, France (Other)

1,300

Enrollment

Locations

120

Anticipated Duration (Months)

650

Patients Per Site

5.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The family of inflammatory/autoimmune systemic diseases (IAD) form a continuum from pure inflammatory diseases to pure autoimmune diseases, encompassing a large panel of inflammatory diseases with some autoimmune components, and vice versa. Cross phenotyping of patients with IAD should be heuristic and help revise the nosography and the understanding of these diseases.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteer Rheumatoid Arthritis Ankylosing Spondylitis Systemic Lupus Erythematosus/Antiphospholipid Syndrome FMF Cryopyrin-Associated Periodic Syndromes /TNF-receptor Associated Periodic Syndrome Vasculitis Uveitis Myositis Crohn's Disease Ulcerative Rectocolitis Type 1 Diabetes Unclassified IAD Knee and/or Hip Arthritis, Muscular Dystrophy	Other: 1: AID groups Other: 2: Control groups

Detailed Description

The family of inflammatory/autoimmune systemic diseases (IAD) represents a large group of human diseases. For most if not all of these IAD, the pathophysiological processes or exact causes remain poorly understood. Progresses in molecular understanding of these IAD have led to realize that these are not two distinct categories of diseases. Rather they form a continuum from pure inflammatory diseases to pure autoimmune diseases, encompassing a large panel of inflammatory diseases with some autoimmune components, and vice versa.

Using systems biology, the investigator aims to improve the understanding of these diseases, to identify novel genes/pathways involved, specific or across the diseases, and to discover biomarkers and potential therapeutic targets.

The investigator will study adult patients with at least one of the following IAD: Rheumatoid Arthritis, Ankylosing Spondylitis, Systemic Lupus Erythematosus/Antiphospholipid Syndrome, Familial Mediterranean Fever (FMF), Cryopyrin-Associated Periodic Syndromes (CAPS) /Tumor Necrosis Factor-receptor Associated Periodic Syndrome (TRAPS), Vasculitis, Uveitis, Myositis, Crohn's Disease, Ulcerative colitis, Type 1 Diabetes. This panel will be completed by controls groups: healthy volunteers, and patients with arthritis (knee and/or hip) or muscular dystrophy.

The biological investigations will notably comprise: immunomics (comprehensive evaluation of peripheral blood cell subsets and serum immunoproteomics, including autoantibodies); transcriptomics; Human Leukocyte Antigen (HLA)-phenotyping; genomics; T-Cell Receptor (TCR) sequencing and microbiota studies.

After signing the informed consent, the subject attends only one visit (Day 0) during which all biological samples will be taken and all clinical information collected.

Study Design

Study Type:

Observational

Anticipated Enrollment :

1300 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Clinical and Multi-omics Cross-phenotyping of Patients With Autoimmune and Auto-inflammatory Diseases

Actual Study Start Date :

Jul 1, 2015

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
1: AID groups Rheumatoid Arthritis, Ankylosing Spondylitis, Systemic Lupus Erythematosus/Antiphospholipid Syndrome, FMF, Cryopyrin-Associated Periodic Syndromes (CAPS)/TNF-receptor Associated Periodic Syndrome (TRAPS), Vasculitis, Uveitis, Myositis, Crohn's Disease, Ulcerative colitis, Type 1 Diabetes	Other: 1: AID groups Clinical and Biological investigations
2: Control groups knee arthritis, hip arthritis, muscular dystrophy, healthy subject	Other: 2: Control groups Clinical and Biological investigations

Arm

Intervention/Treatment

1: AID groups

Rheumatoid Arthritis, Ankylosing Spondylitis, Systemic Lupus Erythematosus/Antiphospholipid Syndrome, FMF, Cryopyrin-Associated Periodic Syndromes (CAPS)/TNF-receptor Associated Periodic Syndrome (TRAPS), Vasculitis, Uveitis, Myositis, Crohn's Disease, Ulcerative colitis, Type 1 Diabetes

Other: 1: AID groups

Clinical and Biological investigations

2: Control groups

knee arthritis, hip arthritis, muscular dystrophy, healthy subject

Other: 2: Control groups

Clinical and Biological investigations

Outcome Measures

Primary Outcome Measures

Total peripheral blood gene expression between patients, expressed as fluorescence intensity [at day 0, no follow-up]
Identification of novel molecular and cellular pathways involved either in specific diseases or across the IAD continuum through a multiparametric approach
Tregs and Tconvs T cell receptor repertoire, expressed as the % of unique TCR sequences [at day 0, no follow-up]
Identification of novel molecular and cellular pathways involved either in specific diseases or across the IAD continuum through a multiparametric approach
HLA type and SNPs expressed as the occurrence events across patients [at day 0, no follow-up]
Identification of novel molecular and cellular pathways involved either in specific diseases or across the IAD continuum through a multiparametric approach
Microbiote species identification expressed as the % of species per family and genus [at day 0, no follow-up]
Identification of novel molecular and cellular pathways involved either in specific diseases or across the IAD continuum through a multiparametric approach
Cytokines and chemokines expressed as fluorescence intensity [at day 0, no follow-up]
Identification of novel molecular and cellular pathways involved either in specific diseases or across the IAD continuum through a multiparametric approach
Immune cells phenotyping expressed as the each cell type % within total PBMCs [at day 0, no follow-up]
Identification of novel molecular and cellular pathways involved either in specific diseases or across the IAD continuum through a multiparametric approach

Secondary Outcome Measures

Changes in gene expression intensity between patients and healthy controls - for each Disease cohorts [at day 0, no follow-up]
Identification of new biomarkers and potential therapeutic by multiscale analysis
Changes in Tregs and Tconvs TCR sequence frequencies between patients and healthy controls - for each Disease cohorts [at day 0, no follow-up]
Identification of new biomarkers and potential therapeutic by multiscale analysis
Characterization of HLA and SNP profiles in patients and healthy controls - for each Disease cohorts [at day 0, no follow-up]
Identification of new biomarkers and potential therapeutic by multiscale analysis
Changes in Microbiote composition between patients and healthy controls - for each Disease cohorts [at day 0, no follow-up]
Identification of new biomarkers and potential therapeutic by multiscale analysis
Changes in cytokines and chemokines expression levels between patients and healthy controls - for each Disease cohorts [at day 0, no follow-up]
Identification of new biomarkers and potential therapeutic by multiscale analysis
Changes in immune cells frequencies between patients and healthy controls - for each Disease cohorts [at day 0, no follow-up]
Identification of new biomarkers and potential therapeutic by multiscale analysis
Identification of specific and common gene expression levels between patients - between Disease cohorts [at day 0, no follow-up]
Identification of new biomarkers and potential therapeutic by multiscale analysis
Identification of specific and common Tregs and Tconvs TCR sequence frequencies between patients - between Disease cohorts [at day 0, no follow-up]
Identification of new biomarkers and potential therapeutic by multiscale analysis
Characterization of specific and common HLA and SNP profiles in patients - between Disease cohorts [at day 0, no follow-up]
Identification of new biomarkers and potential therapeutic by multiscale analysis
Identification of specific and common microbiote composition between patients - between Disease cohorts [at day 0, no follow-up]
Identification of new biomarkers and potential therapeutic by multiscale analysis
Identification of specific and common cytokines and chemokines expression levels between patients - between Disease cohorts [at day 0, no follow-up]
Identification of new biomarkers and potential therapeutic by multiscale analysis
Characterization specific and common variations in immune cells frequencies between patients - between Disease cohorts [at day 0, no follow-up]
Identification of new biomarkers and potential therapeutic by multiscale analysis

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Presenting either:
one IAD from our list (Rheumatoid Arthritis, Ankylosing Spondylitis, Systemic Lupus Erythematosus/Antiphospholipid Syndrome, FMF, Cryopyrin-Associated Periodic Syndromes (CAPS)/Tumor Necrosis Factor (TNF)-receptor Associated Periodic Syndrome, Vasculitis, Uveitis, Myositis, Crohn's Disease, Ulcerative colitis, Type 1 Diabetes)
or an unclassified IAD : a knee and/or hip arthritis or a muscular dystrophy
or healthy subject
Good veins
Affiliation to a social security system
Informed consent form, signed by the participant and the investigator, prior all needed examination

Exclusion Criteria:

For IADs patients
Unauthorized treatment (anticancer chemotherapy)
For Healthy volunteers
Contra-indications for donating blood except from age
Known history of IAD (eg: Psoriasis)
Common exclusion criteria:
Pregnant woman
Still under the exclusion period from another biomedical study
Psychiatric or addiction pathology who could interfere with the ability to fulfill the protocol needs or to provide an informed consent
Patient under a legal protection
Chronic lifelong viral infection unrelated to the pathology
Mild infection within the last 3 months