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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

Objectif

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.

Champ scientifique

Programme(s)

Thème(s)

Appel à propositions

FP7-HEALTH-2010-single-stage
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Régime de financement

CP-FP - Small or medium-scale focused research project

Coordinateur

UNIVERSITETET I BERGEN
Contribution de l’UE
€ 705 849,00
Adresse
MUSEPLASSEN 1
5020 Bergen
Norvège

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Région
Norge Vestlandet Vestland
Type d’activité
Higher or Secondary Education Establishments
Contact administratif
Liv-Grethe Gudmundsen (Mr.)
Liens
Coût total
Aucune donnée

Participants (12)

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Dernière mise à jour: 1 Août 2019

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Permalink: https://cordis.europa.eu/project/id/261460/fr

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