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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

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.

Coordinator

UNIVERSITETET I BERGEN

Address

Museplassen 1
5020 Bergen

Norway

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 705 849

Administrative Contact

Liv-Grethe Gudmundsen (Mr.)

Participants (12)

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UNIWERSYTET JAGIELLONSKI

Poland

EU Contribution

€ 541 741,50

KAROLINSKA INSTITUTET

Sweden

EU Contribution

€ 545 993,80

4 SC AG

Germany

EU Contribution

€ 703 985,60

AARHUS UNIVERSITET

Denmark

EU Contribution

€ 253 504,80

ANAXOMICS BIOTECH, S.L.

Spain

EU Contribution

€ 160 889,20

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

Spain

EU Contribution

€ 503 266,60

THE UNIVERSITY OF BIRMINGHAM

United Kingdom

EU Contribution

€ 447 759,80

UNIVERSITY OF GLASGOW

United Kingdom

EU Contribution

€ 542 663,80

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE

United Kingdom

UNIVERSITA DEGLI STUDI DI FIRENZE

Italy

EU Contribution

€ 433 146,70

GOETEBORGS UNIVERSITET

Sweden

EU Contribution

€ 498 729,60

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

United Kingdom

EU Contribution

€ 514 057,60

Project information

Grant agreement ID: 261460

Status

Closed project

  • Start date

    1 November 2010

  • End date

    31 October 2014

Funded under:

FP7-HEALTH

  • Overall budget:

    € 7 588 334,62

  • EU contribution

    € 5 851 588

Coordinated by:

UNIVERSITETET I BERGEN

Norway