Phenomics in Autoimmune and Inflammatory Diseases

Completed

• Conditions: Healthy Volunteer; Systemic Lupus Erythematosus/Antiphospholipid Syndrome; Ulcerative Rectocolitis; Type 1 Diabetes; Rheumatoid Arthritis; Cryopyrin-Associated Periodic Syndromes /TNF-receptor Associated Periodic Syndrome; Uveitis; FMF; Myositis; Ankylosing Spondylitis

• Registration Number: NCT02466217
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

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 Timeline

• Study First Submitted: 2015-05-12
• Study First Submitted QC: 2015-06-04
• Study First Posted: 2015-06-09
• Study Start: 2015-07-29
• Primary Completion: 2022-07-14
• Study Completion: 2022-07-18
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-07
• Last Update Posted: 2023-08-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 537

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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
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
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
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
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
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

Name	Time	Method
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
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
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
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 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 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 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
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
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
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

Trial Locations

Locations (2)

Rhumatologie - Hôpital Saint-Antoine; 🇫🇷 Paris, France

CIC Paris-Est, Hôpital PITIE SALPETRIERE; 🇫🇷 Paris, France