Karolinska institutet

Principal Investigtors:
Lars Klareskog (coordinator) 
Christina Opava (vice coordinator) 
Johan Askling (vice coordinator) 
Göran Hansson
Rikard Holmdahl
Sven Pettersson

Research group Lars Klareskog

Projects: Etiology, prognosis and therapy in inflammatory joint disease in particular rheumatoid arthritis.

The arthritis research group at Karolinska aims at combining clinical research based on close observation and therapy of large patient groups in our clinic and in a Swedish network. With modern genetic epidemiology we will obtain information about genetic polymorphisms, about environmental and life style exposures and about biomarkers (in particular immunophenotypes) which will be used to understand why individuals get arthritis, what determines the disease course of arthritis, what determines response to therapy and what determines outcome and co-morbidities. This research is done in a team of clinical scientists working closely with patients, with epidemiologists having access to Swedish databases and unique national data sources, with geneticists using modern large scale genetics in collaboration with partners all over the world, and with cell- and molecular immunology where the core is in the laboratory at Center for Molecular Medicine within Karolinska Institutet. Using this strategy, we are presently developing new models for the ethiology of various sub-sets of rheumatoid arthritis. This knowledge will ultimately enable us to develop much more sophisticated therapies.

This strategy also means that several different research groups, lead by independent principal investigators, are involved in the research which is coordinated by PI Lars Klareskog. Participating groups are:

Lars Alfredsson, professor in cardio vascular medicine, Institute of Environmental Medicine, Karolinska Institutet – epidemiology, gene and gene-environment interactions

Johan Askling, rheumatologist and clinical epidemiologist – studies on disease course and outcomes and drug evaluation

Leonid Payukov, geneticist responsible for the genetics laboratory at Center for Molecular Medicine

Anca Catrina, rheumatologist and scientist responsible for studies on molecular mechanisms of the synovial inflammation, destruction and of mechanisms of action of anti-rheumatic drugs, also involved in clinical trials

Vivianne Malmström. cellular immunologist responsible for the cell immunology group at the Center for Molecular Medicine

Ronald van Vollenhoven, associate professor, senior physician – responsible for the clinical treatment and clinical trials unit at the Rheumatology clinic at Karolinska university hospital

Per-Johan Jakobsson, responsible for the proteomics and prostaglandin related work at the Center for Molecular Medicine and the Rheumatology clinic at Karolinska university hospital.

Jon Lampa, rheumatologist, assistant professor – responsible for studies on interactions between the immune system and central nervous system and also involved in clinical trials.

Per Larsson, associate professor at the Rheumatology clinic – responsible for several international collaborations, in particular related to ethiology of arthritis in non-European countries such as Malaysia.

Selected publications.

Klareskog L, Rönnelid J, Lundberg K, Padyukov L, Alfredsson L. Immunity to citrullinated proteins in rheumatoid arthritis. Annu Rev Immunol. 2008;26:651-75

Klareskog L, Stolt P, Lundberg K, Källberg H, Bengtsson C, Grunewald J, Rönnelid J, Erlandsson Harris H, Ulfgren AK, Rantapää-Dahlqvist S, Eklund A, Padyukov L, Alfredsson L. A new model for an etiology of RA; Smoking may trigger HLA-DR (SE)- resticted immune reactions to autoantigens modified by citrullination. Arthritis and Rheumatism 2006;54(1):38-46.

Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW, de Bakker PI, Le JM, Lee HS, Batliwalla F, Li W, Masters SL, Booty MG, Carulli JP, Padyukov L, Alfredsson L, Klareskog L, Chen WV, Amos CI, Criswell LA, Seldin MF, Kastner DL, Gregersen PK. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med. 2007 Sep 6;357(10):977-86.

Klareskog L, Padyukov L, Rönnelid J, Alfredsson L. Genes, environment and immunity in the development of rheumatoid arthritis. Curr Opin Immunol. 2006 Dec;18(6):650-5. Epub 2006 Sep 28.

Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, Martin Mola E, Pavelka K, Sany J, Settas L, Wajdula J, Pedersen R, Fatenejad S, Sanda M; TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004 Feb 28;363(9410):675-81.

Group M Wahren Herlenius:

We study the role of B lymphocytes in autoimmune rheumatic diseases with the aim to understand pathogenic processes and identify targets for therapeutic intervention. The conditions we take specific interest in are Sjögren's syndrome and congenital heart block. Our research has a translational approach and involves both basic molecular studies, analysis in experimental models and clinical investigations.

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Research group Professor Göran K. Hansson

Principal Investigator, Head of the Cardiovascular Research Unit

Our research is focused on immune mechanisms in atherosclerosis development. Atherosclerosis is an inflammatory disease. The disease is associated with systemic immune responses and signs of inflammation. Its lesions are filled with immune cells that can orchestrate and effect inflammatory responses. In fact, the first lesions of atherosclerosis consist of macrophages and T cells. Unstable plaques are particularly rich in activated immune cells, suggesting that they may initiate plaque activation. Experiments in gene-targeted mice have provided mechanistic evidence that immune mechanisms are involved in atherosclerosis.

During recent years, we have seen a rapid increase in understanding of the mechanisms that govern the recruitment, differentiation and activation of immune cells in atherosclerosis. Experimental research has identified several candidate antigens and there is encouraging data suggesting that immune modulation as well as immunization can reduce the progression of the disease.


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