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Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases

Objective

We concur to the IMI on “Reclassification of SLE, connective tissue diseases and RA” call by presenting a proposal aimed at using the power of OMICs, and bioinformatics to identify new classifications for diseases known to share common pathophysiological mechanisms. Such knowledge has not been applied to individual patients, depriving them from potential benefits in terms of the use of new therapeutic agents that are being developed for one disease but cannot be applied in another due to current clinical classifications.
We will investigate individuals with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren’s syndrome (Sjs), rheumatoid arthritis (RA), primary antiphospholipid syndrome (PAPS) and mixed connective tissue disease (MCTD), jointly as systemic autoimmune diseases (SADs). We believe that there will be overlapping clusters of individuals across diseases that will share molecular features. To determine these clusters we will, study 2000 cases of SADs, and 600 healthy controls to identify molecular clusters and their cellular and clinical correlates. In addition, we will study kidney and skin biopsies to define the development of molecular markers with severe kidney disease or with skin fibrosis. In this way we will define systemic and tissue taxonomies. We will study complete as well as isolated peripheral blood mononuclear cells and subpopulations and in biopsies gene expression and epigenetic marks with a combination of array and next generation sequencing (NGS) strategies. These studies will define cellular counts and proportions and changes in gene expression related to specific cellular populations. We will also use NGS strategies to define the presence of risk alleles (HLA and non-HLA) in all individuals. The data will be complemented with the study of the presence of autoantibodies in serum (analyzed in a reference lab), and we will use metabolomics mass spectrometry and NMR approaches to analyze plasma and urine metabolites. We will also study exosomes in plasma and urine and identify their molecular profiles. Samples will be collected following strict protocols and appropriate patient selection. The bioinformatics and biostatistics approaches will be aimed at the analysis of clusters with unsupervised clustering algorithms and tools and cross-validation. We will also perform analyses to determine risk and predictive models analyzing the genetic and molecular data at different levels, leading to a highly productive study with two arms, one for basic research and one with clinical applications. Among the clinical applications we will have a new classification for groups of patients sharing molecular mechanisms of disease, biomarkers for disease progression and organ damage prediction, and we will develop assays that can be easily applied in the clinic. The resultant clinically applicable clusters will be then validated in a longitudinal, inception trial where newly recruited patients will be analyzed at baseline and at two different time points and define their clustering status or their evolution towards specific clusters.
We will gain completely novel information that will open new avenues of research and new possibilities of collaboration between the public Academy and the private Pharmaceutical sector by establishing the basis for new clinical trials with the potential to really benefit the patients.

Call for proposal

IMI-JU-08-2012
See other projects for this call

Coordinator

UCB BIOPHARMA
Address
Allee De La Recherche 60
1070 Bruxelles
Belgium

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Principal investigator
John Ioannou (Dr)
Administrative Contact
Katharina Klapper (Mrs)

Participants (28)

FUNDACION PUBLICA ANDALUZA PROGRESO Y SALUD M.P.
Spain
EU contribution
€ 1 826 852
Address
Avenida Americo Vespucio 15 Edif S2
41092 Sevilla

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Activity type
Research Organisations
Administrative Contact
Enrique Sanchez Suarez (Mr.)
ATRYS HEALTH, SA
Spain
EU contribution
€ 243 425
Address
Calle Velazquez 24 4 Izquierda
28001 Madrid

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Encarna Vega (Mr.)
CENTRO HOSPITALAR UNIVERSITARIO DO PORTO EPE
Portugal
EU contribution
€ 153 324
Address
Largo Professor Abel Salazar
4099 001 Porto

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Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Administrative Contact
Ana Isabel Tavares (Ms)
AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain
EU contribution
€ 846 180
Address
Calle Serrano 117
28006 Madrid

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Activity type
Research Organisations
Administrative Contact
María Requejo (Mrs)
FONDAZIONE IRCCS CA' GRANDA - OSPEDALE MAGGIORE POLICLINICO
Italy
EU contribution
€ 388 612
Address
Via Francesco Sforza 28
20122 Milano

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Activity type
Other
Administrative Contact
Manuela Martorana (MRS)
FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE
Spain
EU contribution
€ 1 026 782
Address
Avenida Gran Via Hospitalet 199-203
08908 L'hospitalet De Llobregat

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Activity type
Research Organisations
Administrative Contact
LAIA LAGUNAS (MRS.)
Servicio Cántabro de Salud
Spain
EU contribution
€ 127 950
Address
Avenida De Cardenal Herrera Oria
Santander

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Activity type
Research Organisations
Administrative Contact
Raquel Leal (Technician)
CONSORCI INSTITUT D'INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER
Spain
EU contribution
€ 145 320
Address
Calle Rossello 149 Puerta Bjs
08036 Barcelona

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Activity type
Other
Administrative Contact
Pastora Martínez Samper (Dr.)
KAROLINSKA INSTITUTET
Sweden
EU contribution
€ 434 450
Address
Nobels Vag 5
17177 Stockholm

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Anna Frostegård (MD, PhD, Leg.Läk)
KATHOLIEKE UNIVERSITEIT LEUVEN
Belgium
EU contribution
€ 229 400
Address
Oude Markt 13
3000 Leuven

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Karolien Mariën (Ms)
KLINIKUM DER UNIVERSITAET ZU KOELN
Germany
EU contribution
€ 129 800
Address
Kerpener Strasse 62
50937 Koeln

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Petra Schreiner-Kaub (Mrs)
MEDIZINISCHE HOCHSCHULE HANNOVER
Germany
EU contribution
€ 217 924
Address
Carl-neuberg-strasse 1
30625 Hannover

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Simone Hess (Dr)
MEDIZINISCHE UNIVERSITAET WIEN
Austria
EU contribution
€ 45 520
Address
Spitalgasse 23
1090 Wien

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Michaela Ernst (Mrs)
Quartz Bio S.A.
Switzerland
EU contribution
€ 893 562
Address
Chemin Du Pré-fleuri
1228 Plan-les-ouates

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Administrative Contact
Jérôme Wojcik (CEO)
SERVICIO ANDALUZ DE SALUD
Spain
EU contribution
€ 556 740
Address
Avenida De La Constitucion 18
41071 Sevilla

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Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Administrative Contact
Elena Martin-Bautista (Dr)
KYPRIAKO IDRYMA EREVNON GIA TI MYIKI DISTROFIA
Cyprus
EU contribution
€ 252 540
Address
6 Iroon Avenue
2371 Agios Dometios

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Activity type
Research Organisations
Administrative Contact
Marios Flouros (Mr.)
UNIVERSIDAD DE GRANADA
Spain
EU contribution
€ 480 780
Address
Cuesta Del Hospicio Sn
18071 Granada

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Jose A. Carrillo Miñán (Mr)
UNIVERSITA DEGLI STUDI DI MILANO
Italy
EU contribution
€ 254 040
Address
Via Festa Del Perdono 7
20122 Milano

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Anna Maria Cerini (Mrs)
UNIVERSITE CATHOLIQUE DE LOUVAIN
Belgium
EU contribution
€ 341 995
Address
Place De L Universite 1
1348 Louvain La Neuve

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Geneviève Depresseux (Mrs.)
UNIVERSITE DE BRETAGNE OCCIDENTALE
France
EU contribution
€ 638 199
Address
Rue Des Archives 3
29238 Brest

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Nathalie Queffelec (Ingénieur Europe)
UNIVERSITE DE GENEVE
Switzerland
EU contribution
€ 270 140
Address
Rue Du General Dufour 24
1211 Geneve

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Carlo CHIZZOLINI (Dr.)
SZEGEDI TUDOMANYEGYETEM
Hungary
EU contribution
€ 67 350
Address
Dugonics Ter 13
6720 Szeged

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Gabor Antal (-)
Deutsches Rheuma-Forschungszentrum Berlin

Participation ended

Germany
EU contribution
€ 49 453
Address
Chariteplatz 1
10117 Berlin
Activity type
Research Organisations
Administrative Contact
Petra Starke (-)
BAYER AKTIENGESELLSCHAFT
Germany
Address
Kaiser-wilhelm-allee 1
51373 Leverkusen

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Petra Freitag (Mr.)
INSTITUT DE RECHERCHES INTERNATIONALES SERVIER IRIS
France
Address
Rue Carnot 50
92284 Courbevoie

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Marie DUVICQ (Ms)
SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT
France
Address
Pierre Brossolette 1
91380 Chilly Mazarin

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Thorsten Strube (Dr.)
ELI LILLY AND COMPANY LTD
United Kingdom
Address
Lilly House Basingview
RG21 4FA Basingstoke

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Birgit Steckel-Hamann (Dr)
CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Germany
EU contribution
€ 378 985
Address
Chariteplatz 1
10117 Berlin

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Eveline Fräßdorf (Ms)