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Protein citrullination as a link between periodontal diseases and rheumatoid arthritis (RA) and target for development of novel drugs to treat RA

Objective

Autoimmunity in rheumatoid arthritis (RA) is characterised by an antibody response to citrullinated proteins. Periodontitis (PD) is largely caused by infection, in which
Porphyromonas gingivalis is a major pathogen. The two diseases combine specific HLA-DRB1alleles and smoking as risk factors, and have a similar pathophysiology characterised by destructive inflammation. A possible causative link between RA and PD is based on the ability of P. gingivalis to citrullinate proteins and thereby generate autoantigens that drive autoimmunity in RA. We hypothesise that anti-citrullinated protein antibodies can be generated, in genetically susceptible individuals, as a consequence of P. Gingivalis-induced citrullination in the gingiva. In the context of genetic risk factors, during chronic exposure to danger signals, such as bacterial
lipopolysacharides and DNA, tolerance to citrullinated proteins may be broken, with production of a pathogenic antibody response, which at a later time point cross-reacts with joint proteins and causes chronic RA. We will use a multidisciplinary approach (genetics, epidemiology, molecular immunology and animal models) to study susceptibility factors and immune responses in RA and PD, with an aim to identify novel etiological and pathogenic pathways, forming the basis for new therapies.

Call for proposal

FP7-HEALTH-2010-single-stage
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Coordinator

UNIVERSITETET I BERGEN
Address
Museplassen 1
5020 Bergen
Norway

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Liv-Grethe Gudmundsen (Mr.)
EU contribution
€ 705 849

Participants (12)

Jagiellonian University in Krakow
Poland
EU contribution
€ 541 741,50
Address
Ul. Golebia 24
31007 Krakow

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Agata Potempa (Ms.)
KAROLINSKA INSTITUTET
Sweden
EU contribution
€ 545 993,80
Address
Nobels Vag 5
17177 Stockholm

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Caroline Hamilton (Ms.)
4 SC AG
Germany
EU contribution
€ 703 985,60
Address
Fraunhoferstr. 22
82152 Planegg Martinsried

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Enno Spillner (Mr.)
AARHUS UNIVERSITET
Denmark
EU contribution
€ 253 504,80
Address
Nordre Ringgade 1
8000 Aarhus C

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Leth Stentov Pernille
ANAXOMICS BIOTECH SL
Spain
EU contribution
€ 160 889,20
Address
Calle Diputacio 237, P 1 Pta 1
08007 Barcelona

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Vesna Radovanovic (Ms.)
AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain
EU contribution
€ 503 266,60
Address
Calle Serrano 117
28006 Madrid

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Activity type
Research Organisations
Administrative Contact
Eusebio Jimenez Arroyo (Mr.)
THE UNIVERSITY OF BIRMINGHAM
United Kingdom
EU contribution
€ 447 759,80
Address
Edgbaston
B15 2TT Birmingham

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Robert Fekete (Mr.)
UNIVERSITY OF GLASGOW
United Kingdom
EU contribution
€ 542 663,80
Address
University Avenue
G12 8QQ Glasgow

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Joe Galloway (Mr.)
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE

Participation ended

United Kingdom
Address
South Kensington Campus Exhibition Road
SW7 2AZ London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Tatjana Palalic (Ms.)
UNIVERSITA DEGLI STUDI DI FIRENZE
Italy
EU contribution
€ 433 146,70
Address
Piazza San Marco 4
50121 Florence

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Pier Remigio Salvi (Prof.)
GOETEBORGS UNIVERSITET
Sweden
EU contribution
€ 498 729,60
Address
Vasaparken
405 30 Goeteborg

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Emilia Rung (Dr.)
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
EU contribution
€ 514 057,60
Address
Wellington Square University Offices
OX1 2JD Oxford

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Linda Pialek (Ms.)