Clinical Trial: Phenomics in Autoimmune and Inflammatory Diseases

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

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

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 Summary:

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 t
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome:

  • Total peripheral blood gene expression between patients, expressed as fluorescence intensity [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Changes in gene expression intensity between patients and healthy controls - for each Disease cohorts [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: at day 0, no follow-up ]
      Identification of new biomarkers and potential therapeutic by multiscale analysis


    Original Secondary Outcome: Same as current

    Information By: Assistance Publique - Hôpitaux de Paris

    Dates:
    Date Received: May 12, 2015
    Date Started: July 2015
    Date Completion: July 2021
    Last Updated: December 12, 2016
    Last Verified: December 2016