PRECISESADST: Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: Case-control
Study Details
Study Description
Brief Summary
Connective tissue diseases (CTD) or systemic autoimmune diseases (SADs) as they are known today are a group of chronic inflammatory conditions with autoimmune aetiology with few treatment options and difficult diagnosis.Brest team contribute to perform a new classification of the following systemic autoimmune diseases in a European Union's Seventh Framework Programme. The aim of this research is to constitute a Healthy Volunteers cohort to compare with systemic autoimmune diseases cohort into molecular clusters instead of clinical entities through the determination of molecular profiles using several "Omics" techniques.
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Detailed Description
The main objective of the PRECISESADS project is to reclassify the individuals affected by SADs into molecular clusters instead of clinical entities through the determination of molecular profiles using several "-omics" techniques.
The specific objectives of this cross sectional study and sub-study are:
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To identify a systemic taxonomy for patients with SADs by producing the following data in individuals with SADs and controls: genetic, epigenomic, transcriptomic, flow cytometric (from peripheral blood mononuclear and polymorphonuclear cells (PBMCs)), metabolomics and proteomic in plasma and urine, exosome analysis, classical serology (antibodies and autoantibodies), and clinical data.
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To better characterize individual SADs at the omics level.
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To perform clustering analyses to determine the groups of individuals who, differentially from other groups, share specific molecular features (precision medicine).
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To identify gene expression, methylation profiles through deconvolution methods comparing a mixture of cells with subpopulations determined by flow cytometry with separated cells, cytokine profiles and plasma metabolomics using Mass Spectrometry, in a substudy of 288 individuals.
The clustering process will be data-driven with the aim to find the most homogenous and differentiated clusters of diseases that clearly separate individuals on the basis of, serological, genetic, epigenomic, cellular (cell proportions), metabolomic, proteomic (cytokines, autoantibodies) and transcriptome characteristics and differentiate them from controls and other patient clusters.
A total of 2000 patients and 666 controls will be included in the study.
Study Design
Outcome Measures
Primary Outcome Measures
- Gene expression in total blood [2 years]
Gene expression will be done using commercial gene expression microarrays in total blood from all samples using the RNA Paxgene tube.
- Flow cytometry analysis to determine cell proportions in the total blood mixture in all individuals. [24 hours]
9 optimized panels of antibodies will be used to determine cell subpopulations in peripheral blood (including very minor cell populations).
- Genotyping [2 years]
Genotyping will be done using a whole genome array.
- Metabolite determination [2 years]
Metabolite determination in plasma and urine using Nuclear Magnetic Resonance
- Exosome isolation from plasma and urine [2 years]
set up of the methodology for isolating exosomes in these bodily fluids for gene expression analysis
- Cytokine profile determination [2 years]
88 different cytokines will be assessed with Luminex
- routine autoantibodies in serum [2 years]
set of serum autoantibodies will be determined in a European validated laboratory. Also, they will perform detection of antibodies against small lipid moieties i.e.antiphosphorylcholine), lupus anticoagulant and complement proteins in plasma.
- Gene expression methylation in total blood [2 years]
Methylation analysis will be done using the methylome 450k array using the DNA obtained from total blood. MicroRNA gene expression arrays using total blood.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Aged 18 years or older at the time of consent
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Signed the informed consent form
Exclusion Criteria:
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Individuals on chronic medication.
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Individuals suffering from any inflammatory, autoimmune, allergic or infectious condition and if possible without a history of autoimmune disease, particularly thyroid disease or other diseases that may modify cellular profiles in blood.
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Pregnant women.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical University of Vienna | Vienna | Austria | ||
| 2 | UZ Leuven - KU Leuven, Department of Rheumatology (KU LEUVEN) | Leuven | Belgium | ||
| 3 | CHRU de Brest | Brest | France | 29609 | |
| 4 | Deutsches Rheuma-Forschungszentrum Berlin (DRFZ) | Berlin | Germany | ||
| 5 | Medizinische Hochschule Hannover | Hannover | Germany | ||
| 6 | University of Szeged | Szeged | Hungary | ||
| 7 | Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico (IRCCS) | Milan | Italy | ||
| 8 | UNIMI, Istituto Ortopedico Getano Pini | Milan | Italy | ||
| 9 | Centro Hospitalar do Porto | Porto | Portugal | ||
| 10 | Hospital Clinic I Provicia- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) | Barcelona | Spain | ||
| 11 | Hospital Universitario Reina Sofía Andaluz de Salud | Cordoba | Spain | ||
| 12 | Biobanco del Sistema Sanitario Público de Andalucía (SSPA) | Granada | Spain | ||
| 13 | Hospital Universitario San Cecilio Servicio Andaluz de Salud | Granada | Spain | ||
| 14 | Hospital Virgen de las Nieves Granada | Granada | Spain | ||
| 15 | Hospital Regional de Málaga Servicio Andaluz de Salud | Malaga | Spain | ||
| 16 | Hospital Universitario Marqués de Valdecilla, Servicio Cántabro de Salud | Santander | Spain | ||
| 17 | Hospitaux Universitaires de Géneve | Geneve | Switzerland |
Sponsors and Collaborators
- Fundación Pública Andaluza Progreso y Salud
- UCB Biopharma S.P.R.L.
- Atrys Health
- National Research Council, Spain
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
- Servicio Cántabro de Salud
- August Pi Sunyer Biomedical Research Institute
- Karolinska Institutet
- KU Leuven
- Klinikum der Universität Köln
- Hannover Medical School
- Medical University of Vienna
- Quartz Bio S.A.
- Andaluz Health Service
- The Cyprus Foundation for Muscular Dystrophy Research
- Universidad de Granada
- University of Milan
- Université Catholique de Louvain
- University Hospital, Brest
- University of Geneva, Switzerland
- Szeged University
- Bayer
- Institut de Recherches Internationales Servier
- Sanofi
- Eli Lilly and Company
- Charite University, Berlin, Germany
- Centro Hospitalar do Porto
- Institut d'Investigació Biomèdica de Bellvitge
- Innovative Medicines Initiative
Investigators
- Study Director: Marta Alarcon, Fundación Pública Andaluza Progreso y Salud (PHFSpain)
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PRECISESADS-T