Ziel
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.
Wissenschaftliches Gebiet
- medical and health sciencesclinical medicinerheumatology
- medical and health scienceshealth sciencespublic healthepidemiology
- medical and health sciencesbasic medicinephysiologypathophysiology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicineimmunology
Programm/Programme
Aufforderung zur Vorschlagseinreichung
FP7-HEALTH-2010-single-stage
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Finanzierungsplan
CP-FP - Small or medium-scale focused research projectKoordinator
5020 Bergen
Norwegen
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Beteiligte (12)
31007 KRAKOW
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17177 Stockholm
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82152 PLANEGG MARTINSRIED
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8000 Aarhus C
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08007 Barcelona
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28006 Madrid
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B15 2TT Birmingham
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G12 8QQ Glasgow
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SW7 2AZ LONDON
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50121 Florence
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405 30 Goeteborg
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OX1 2JD Oxford
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