The Pathobiology of Autoantibodies in Rheumatoid Arthritis

The Pathobiology of Autoantibodies in Rheumatoid Arthritis

Our research aims to increase our understanding of the pathobiology underpinning the anti-citrullinated protein/peptide antibody (ACPA) response in rheumatoid arthritis (RA). Specifically, we investigate the hypothesis that the periodontal bacterium Porphyromonas gingivalis – a major cause of chronic periodontitis – is driving disease in a subset of RA, by mediating loss of tolerance to citrullinated proteins. Furthermore, we aim to determine whether ACPA are pathogenic, and by which mechanisms.

The discovery of autoantibodies directed to citrullinated proteins/peptides (ACPA) 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 the major environmental risk factor, 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.  We have previously shown that ACPA 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.

We hypothesise that Porphyromonas gingivalis, in the context of cigarette smoking and PAMPS (e.g. LPS), drives a local inflammation in the gingival tissue (i.e. gingivitis / periodontitis), triggering the activation of bacterial and human PAD enzymes, which in turn cause increased protein citrullination. In genetically predisposed individuals (i.e. HLA-DRB1 SE+, PTPN22+), citrulline-specific T cells become activated and mediate “help” to ACPA-specific B cells, which in response secrete ACPA. Through epitope-spreading, ACPA later cross-react with citrullinated epitopes in the joint, form immune complexes and drive a local synovial inflammation into a chronic state (i.e. RA). 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. The long-term ambition with our research is to develop personalised antigen-specific therapies and pre-clinical interventions.



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Vårt swish nummer är: 1232457976

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BG 628-4418
PG 514114-8

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Om du befinner dig utanför Sverige, vänligen använd följande information:

Bank: SEB, Stockholm, Sweden
Kontonummer: 5201-11 370 12
Iban-nummer: SE16 5000 0000 0520 1113 7012
Bic-kod (bankens elektroniska adress): ESSESESS
Kontoinnehavare: Stiftelsen Centrum för Molekylär Medicin
L8:05, Karolinska Universitetssjukhuset
171 76 Stockholm, Sweden



Team leader

Karin Lundberg



Associate Professor





Infection and inflammation




Antibodies, Autoimmunity, Biomarkers, Cohort study, Peptides, Proteins, Translational