Rheumatology

Research Teams

• Lars Klareskog

  Arthritis; pathogenesis and therapy

  The arthritis group aims to understand why arthritis occurs in order to allow prevention, and to understand how arthritis occurs in order to improve therapy. We combine clinical research and experimental research in several well integrated research teams at CMM and in extensive international networks.

• Vivianne Malmström

  Cellular immunology and rheumatic diseases

  We study adaptive immune responses (T and B cells) in patients with inflammatory rheumatic diseases to understand initiating events (e.g. defining relevant autoantigens) and the role of such immune responses in disease propagation and therapy response.

• Leonid Padyukov

  Genetics of rheumatic and other inflammatory diseases

  Our group is working on investigation of genetic mechanisms of human inflammatory disease.

• Helena Erlandsson Harris

  Pediatric Rheumatology

  We study innate inflammatory mechanisms active in arthritis. In particular we focus on an Alarmin, the endogenous danger molecule HMGB1, its inflammatory properties and its potential as a new target for anti-inflammatory therapy.

• Anca Catrina

  Synovial Biology

  We are a mixed team of basic scientists and clinicians working together to better understand the inflammatory and destructive process at the site of inflammation in chronic inflammatory joint diseases, with a special focus on rheumatoid arthritis.

• Elisabeth Svenungsson

  Systemic autoimmune diseases and cardiovascular disease

  Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a striking female predominance (90%). Autoantibodies, which target nuclei and membranes of human cells, are immunological characteristics of SLE and deposits of immune complexes can be detected in affected organs.

• Karin Lundberg

  Understanding Specific Autoimmune Reactions that Cause Arthritis

   

  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.

  Anti-CCP antibodies represent the most disease-specific (98%) serological marker for RA. Present in 60%-70% of patients, it divides 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.

  The research in our group is focused on citrullinated α-enolase as a prototype antigen, for investigating the etiology and the pathobiology of the ACPA response. We have previously demonstrated the presence of citrullinated -enolase in the rheumatoid joint, identified the immunodominant B cell epitope (denoted CEP-1), and shown that autoantibodies to citrullinated -enolase is present in 40% of RA patients. We have also demonstrated that genetic risk factors and smoking mainly represent risk factors for CEP-1 positive disease, rather than CCP positive disease. Furthermore, that human anti-CEP-1 antibodies, purified from RA patients, cross-react with citrullinated enolase from the periodontal bacterium Porphyromonas gingivalis, providing a basis for a possible triggering of autoimmunity by molecular mimicry.

  Hypothesis

   

  Aims:

  We aim to determine whether microbes associated with chronic periodontitis (i.e. Porphyromonas gingivalis) may be driving the ACPA response in a subset of RA. This part of our research integrates with three larger European consortia (Gums&Joints, RAPID and TRIGGER). We also aim to determine whether ACPAs are pathogenic, which fine-specificity mediates disease, and by which mechanisms.