Phenomics in Autoimmune and Inflammatory Diseases (TRANSIMMUNOM)

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis; Uveitis; Vasculitis; Type 1 Diabetes; Crohn's Disease; Myositis; Healthy Volunteer; Ankylosing Spondylitis; FMF; Systemic Lupus Erythematosus/Antiphospholipid Syndrome; Cryopyrin-Associated Periodic Syndromes /TNF-receptor Associated Periodic Syndrome; Ulcerative Rectocolitis; Unclassified IAD Knee and/or Hip Arthritis, Muscular Dystrophy
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 537

Contacts and Locations

• Study Contact: Name: David KLATZMANN, MD, PhD; Phone Number: 0033 1 42 17 74 61; Email: david.klatzmann@upmc.fr
• Study Contact Backup: Name: Roberta LORENZON, MD; Phone Number: 33 1 42 17 85 33; Email: roberta.lorenzon@upmc.fr

Study Locations

• France
  • Paris, France, 75012
    • Rhumatologie - Hôpital Saint-Antoine
  • Paris, France, 75013
    • CIC Paris-Est, Hôpital PITIE SALPETRIERE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The investigator will study adult patients with at least one of the following IAD: 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. This panel will be completed by controls groups: healthy volunteers, and patients with arthritis (knee and/or hip) or muscular dystrophy

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: National Research Agency, France
• Investigators: Principal Investigator: David KLATZMANN, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Lorenzon R, Mariotti-Ferrandiz E, Aheng C, Ribet C, Toumi F, Pitoiset F, Chaara W, Derian N, Johanet C, Drakos I, Harris S, Amselem S, Berenbaum F, Benveniste O, Bodaghi B, Cacoub P, Grateau G, Amouyal C, Hartemann A, Saadoun D, Sellam J, Seksik P, Sokol H, Salem JE, Vicaut E, Six A, Rosenzwajg M, Bernard C, Klatzmann D. Clinical and multi-omics cross-phenotyping of patients with autoimmune and autoinflammatory diseases: the observational TRANSIMMUNOM protocol. BMJ Open. 2018 Aug 30;8(8):e021037. doi: 10.1136/bmjopen-2017-021037.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2015
• Primary Completion (Actual): July 14, 2022
• Study Completion (Actual): July 18, 2022

Study Registration Dates

• First Submitted: May 12, 2015
• First Submitted That Met QC Criteria: June 4, 2015
• First Posted (Estimated): June 9, 2015

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Auto-immune disease; Auto-inflammatory disease; Omics; System biology
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Skin Diseases; Infections; Immune System Diseases; Autoimmune Diseases; Hypersensitivity, Immediate; Eye Diseases; Disease Attributes; Disease; Gastrointestinal Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Gastroenteritis; Muscular Diseases; Neuromuscular Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Uveal Diseases; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Skin Diseases, Vascular; Hypersensitivity; Muscular Disorders, Atrophic; Spinal Diseases; Bone Diseases; Inflammatory Bowel Diseases; Spondylarthropathies; Spondylarthritis; Bone Diseases, Infectious; Ankylosis; Urticaria; Colitis; Chronic Disease; Sigmoid Diseases; Proctitis; Chronic Inducible Urticaria; Chronic Urticaria; Axial Spondyloarthritis; Syndrome; Arthritis; Lupus Erythematosus, Systemic; Muscular Dystrophies; Crohn Disease; Myositis; Vasculitis; Antiphospholipid Syndrome; Uveitis; Spondylitis; Spondylitis, Ankylosing; Cryopyrin-Associated Periodic Syndromes; Proctocolitis
• Other Study ID Numbers: P141006; 2015-A00558-41 (Other Identifier: EUDRACT)