Faculty of Medicine

Lund University

Fibrosis and microangiopathy in Systemic Sclerosis (SSc): Pathogenesis, prognostic factors and methods for therapy evaluation.

Principal investigator; Hesselstrand, Roger, Associate Professor, MD/PhD

Clinical speciality: Rheumatology

Phone: +4646177178

Co-workers, Lund University: Andréasson Kristofer, Bjermer Leif, Bozovic Gracijela, Heinegård Dick, Rådegran Göran, Rydell-Törmänen Kristina, Sandqvist Gunnel, Saxne Tore, Scheja Agneta, Tufvesson Ellen, Westergren-Thorsson Gunilla, Wuttge Dirk

International networks: Genetics: Tim Radstake & Javier Martín etc
Biomarkers: Chris Denton, David Abraham, Luc Mouthon, Thomas Krieg, Nicolas Hunzelman etc
Therapy: Ariane Herrick, Oliver Distler, Jörg Distler, Chris Denton, Luc Mouthon, Madelon Vonk, Alan Silman etc
Capillaroscopy: Ariane Herrick, Alberto Sulli, Maurizio Coutolo, Vanessa Smith, Kevin Howell etc

Research area/areas: Rheumatology and Autoimmunity

Systemic sclerosis is a rare rheumatic disease with a poor prognosis. It is characterized by vasculopathy, fibrosis and the production of disease associated autoantibodies. The vasculopathy is associated with an endothelial injury and abnormal vascular tone regulation that results in Raynaud’s phenomenon of fingers, and vascular involvement of lungs or kidneys with resulting pulmonary hypertension or renal crisis. Fibrosis manifests itself with increased synthesis and accumulation of extracellular matrix proteins in skin and internal organs, for example resulting in interstitial lung disease. 10-year survival varies between 40 and 90 percent depending on the subtype of SSc. The major causes of death are pulmonary fibrosis and/or pulmonary arterial hypertension resulting in secondary right heart failure. No cure is available yet and the knowledge about the pathogenesis of SSc is insufficient. Therefore, more research is needed to elucidate the mechanism of vasculopathy, fibrosis and autoimmune inflammation in SSc as well as to improve diagnosis of SSc and therapy evaluation.

In preclinical experiments we address the pathogenetic mechanisms of fibrosis and vasculopathy in lung and skin. Myofibroblasts, epithelial cells and eosinophils are involved in the process. We therefore study the mechanisms of activation via Interleukin-15, COMP, fibromodulin, S100A8/A9, CXCL5 and CXCL8. The experiments involve cell cultures from cell lines and patients, knock out mice, and wild type mice. In addition these markers of activation are further studied as biomarkers in different compartments ie fibrosis or vasculopathy, and in various organs mostly skin and lung.
In clinical cross-sectional and longitudinal studies, we evaluate the role of nailfold capillary microscopy, magnetic resonance imaging of the heart and non-invasive pulmonary function test for diagnosis of SSc and treatment evaluation.

A better understanding of pathogenetic mechanisms and prognostic factors offers better tools for selection of patients for potent therapy and for evaluation of new therapies.

5 recent original publications

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Hesselstrand R, Kassner A, Heinegard D, Saxne T.
COMP a candidate molecule in the pathogenesis of systemic sclerosis with a potential as a disease marker.
Ann Rheum Dis. 2008; 67(9): 1242-8

Wuttge DM, Wildt M, Geborek P, Wollheim FA, Scheja A, Akesson A.
Serum IL-15 in patients with early systemic sclerosis: a potential novel marker of lung disease.
Arthritis Res Ther. 2007; 9: R85

Andréasson Kristofer, Scheja Agneta, Saxne Tore, Ohlsson Bodil, Hesselstrand Roger
Faecal calprotectin: a biomarker of gastrointestinal disease in systemic sclerosis.
Journal of internal medicine. 2010; Dec 12: -

Scheja A, Larsen K, Todorova L, Tufvesson E, Wildt M, Åkesson A, Hansson L, Ellis S, Westergren Thorsson G
BALF derived fibroblasts differ from biopsy derived fibroblasts in systemic sclerosis
Eur Resp J . 2007; 29: 446-452

Wildt M, Wuttge DM, Hesselstrand R, Scheja A
Assessment of capillary density in systemic sclerosis with three different capillaroscopic methods
Clin Exp Rheumatol. ; :

Further publications here (new window)


Total financing:   3.0 MSEK      Gov grant for clinical research ("ALF"):   2.0 MSEK
Total external financing:   1.0 MSEK      Natl and intl prioritized grants:   0.0 MSEK

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