Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: Case-control (PRECISESADST)

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects

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:

1. 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.
2. To better characterize individual SADs at the omics level.
3. To perform clustering analyses to determine the groups of individuals who, differentially from other groups, share specific molecular features (precision medicine).
4. 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 Type: Observational
• Enrollment (Actual): 649

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Medical University of Vienna
• Belgium
  • Leuven, Belgium
    • UZ Leuven - KU Leuven, Department of Rheumatology (KU LEUVEN)
• France
  • Brest, France, 29609
    • CHRU de Brest
• Germany
  • Berlin, Germany
    • Deutsches Rheuma-Forschungszentrum Berlin (DRFZ)
  • Hannover, Germany
    • Medizinische Hochschule Hannover
• Hungary
  • Szeged, Hungary
    • University of Szeged
• Italy
  • Milan, Italy
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico (IRCCS)
  • Milan, Italy
    • UNIMI, Istituto Ortopedico Getano Pini
• Portugal
  • Porto, Portugal
    • Centro Hospitalar do Porto
• Spain
  • Barcelona, Spain
    • Hospital Clinic I Provicia- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
  • Cordoba, Spain
    • Hospital Universitario Reina Sofía Andaluz de Salud
  • Granada, Spain
    • Hospital Universitario San Cecilio Servicio Andaluz de Salud
  • Granada, Spain
    • Hospital Virgen de las Nieves Granada
  • Granada, Spain
    • Biobanco del Sistema Sanitario Público de Andalucía (SSPA)
  • Malaga, Spain
    • Hospital Regional de Málaga Servicio Andaluz de Salud
  • Santander, Spain
    • Hospital Universitario Marqués de Valdecilla, Servicio Cántabro de Salud
• Switzerland
  • Geneve, Switzerland
    • Hospitaux Universitaires de Geneve

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Healthy Volunteers

Description

Inclusion Criteria:

• Aged 18 years or older at the time of consent
• Signed the informed consent form

Exclusion Criteria:

• Individuals on chronic medication.
• 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.
• Pregnant women.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gene expression in total blood	Gene expression will be done using commercial gene expression microarrays in total blood from all samples using the RNA Paxgene tube.	2 years
Flow cytometry analysis to determine cell proportions in the total blood mixture in all individuals.	9 optimized panels of antibodies will be used to determine cell subpopulations in peripheral blood (including very minor cell populations).	24 hours
Genotyping	Genotyping will be done using a whole genome array.	2 years
Metabolite determination	Metabolite determination in plasma and urine using Nuclear Magnetic Resonance	2 years
Exosome isolation from plasma and urine	set up of the methodology for isolating exosomes in these bodily fluids for gene expression analysis	2 years
Cytokine profile determination	88 different cytokines will be assessed with Luminex	2 years
routine autoantibodies in serum	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.	2 years
Gene expression methylation in total blood	Methylation analysis will be done using the methylome 450k array using the DNA obtained from total blood. MicroRNA gene expression arrays using total blood.	2 years

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza Progreso y Salud
• Collaborators: Karolinska Institutet; Eli Lilly and Company; Medical University of Vienna; Sanofi; Bayer; Charite University, Berlin, Germany; Hannover Medical School; KU Leuven; Institut d'Investigació Biomèdica de Bellvitge; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; University Hospital, Brest; Université Catholique de Louvain; Andaluz Health Service; UCB Biopharma S.P.R.L.; Universidad de Granada; Institut de Recherches Internationales Servier; Szeged University; National Research Council, Spain; University of Milan; University of Geneva, Switzerland; Innovative Medicines Initiative; Centro Hospitalar do Porto; Servicio Cántabro de Salud; Atrys Health; August Pi Sunyer Biomedical Research Institute; Klinikum der Universität Köln; Quartz Bio S.A.; The Cyprus Foundation for Muscular Dystrophy Research

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: August 22, 2016
• First Submitted That Met QC Criteria: August 31, 2016
• First Posted (Estimate): September 7, 2016

Study Record Updates

• Last Update Posted (Actual): May 23, 2018
• Last Update Submitted That Met QC Criteria: May 22, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Healthy Volunteers; SADs; Molecular profiles; Omics Techniques
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases
• Other Study ID Numbers: PRECISESADS-T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided