Phenomics in Autoimmune and Inflammatory Diseases

Study Overview
=================
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.

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

Conditions
-----------------
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

Intervention / Treatment
-----------------
* Other: 1: AID groups
* Other: 2: Control groups


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1: AID groups<br>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<br>* Clinical and Biological investigations<br>|
| 2: Control groups<br>knee arthritis, hip arthritis, muscular dystrophy, healthy subject | Other: 2: Control groups<br>* Clinical and Biological investigations<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Auto-immune disease, Auto-inflammatory disease, Omics, System biology