Team Karin Lundberg
The Pathobiology of Autoantibodies in Rheumatoid Arthritis
Our research aims to determine whether the periodontal bacterium Porphyromonas gingivalis may be driving disease in a subset of patients with rheumatoid arthritis (RA), and whether autoantibodies to citrullinated proteins (ACPA), which are associated with this disease subset, are pathogenic
The discovery of autoantibodies directed to citrullinated proteins/peptides has during the past decade increased our understanding of the specific autoimmune reactions that are thought to drive RA, and led to the development of a novel diagnostic test, the CCP ELISA assay. Present in 60%-70% of patients, anti-CCP antibodies divide RA into two disease subsets; the anti-CCP positive and the anti-CCP negative. Well-known genetic risk factors for RA as well as cigarette smoking associate with the anti-CCP positive subset only, which also demonstrates a more destructive disease course. Anti-CCP antibodies are thought to target epitopes on citrullinated proteins in the rheumatoid joint, including citrullinated α-enolase, fibrinogen, vimentin and collagen type II, and thereby drive chronic inflammation. Interestingly, ACPAs targeting citrullinated α-enolase, purified from RA patients, cross-react with citrullinated enolase from Porphyromonas gingivalis, providing a basis for a possible triggering of autoimmunity by molecular mimicry
Work plan and methods
With epidemiological and molecular research approaches, using patient cohorts and biological materials, our research is focused on the studies of citrullinated α-enolase as a prototype citrullinated antigen, for investigating the etiology and the pathogenesis of the ACPA response in RA
Expected impact of results
The long-term ambition with our research is to develop personalised antigen-specific therapies and pre-clinical interventions, targeting P. gingivalis and/or chronic periodontitis
Prof. Patrick Venables, Kennedy Institute of Rheumatology, Oxford, UK
Prof. Jan Potempa, School of Dentistry, University of Louisville, Kentucky, US
Prof. Dominique Baeten, Academic Medical Center, University of Amsterdam, The Netherlands
EU (FP7-People-RAPID and FP7-Health-TRIGGER)
The Swedish Research Council
The Rheumatism Association
KI (Jonas Söderqvist’s foundation, KID Faculty funding from the Board of Research Education, Ulla and Gustaf af Uggla’s foundation, Alex & Eva Wallstöm’s foundation)
Karin Lundberg, group supervisor
Nastya Kharlamova, PhD student
Natalia Sherina, PhD student
Five selected publications
1. Autoimmunity in rheumatoid arthritis: citrulline immunity and beyond.
Adv. Immunol. 2013 ;118():129-58
2. Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis defined by the anticitrullinated protein/peptide antibody fine specificity profile.
Ann. Rheum. Dis. 2013 May;72(5):652-8
3. Periodontitis in RA-the citrullinated enolase connection.
Nat Rev Rheumatol 2010 12;6(12):727-30
4. Specific interaction between genotype, smoking and autoimmunity to citrullinated alpha-enolase in the etiology of rheumatoid arthritis.
Nat. Genet. 2009 Dec;41(12):1319-24
5. Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase.
Arthritis Rheum. 2008 Oct;58(10):3009-19