Pathogenic, diagnostic and therapeutic studies of autoantibody associated systemic vasculitis
Principal investigator; Hellmark, Thomas, Associate Professor, PhD
Co-workers, not Lund University: Segelmark Mårten
Systemic vasculitis is a group of diseases with severe, acute inflammation in the small vessels. The cause of the inflammation is unknown and it occurs without known external influence. Autoantibodies are known to play a role, but this could be from direct attack of the target organ to being markers of the specific inflammation. The clinical picture varies, depending on the organ that is damaged, making the diagnosis difficult. Apparently healthy individuals can within a couple of weeks develop a life threatening disease. We have concentrated on Goodpasture's disease (associated with anti glomerular basement membrane antibodies, anti-GBM), Wegener's granulomatosis and Microscopic polyangiitis (associated with anti neutrophilic cytoplasmatic antibodies, ANCA). This group of diseases is a good model for glomerulonephritis in particular and autoimmunity in general.
Our general aims are: 1. To study the autoantibody epitopes, leukocyte abnormalities, the inflammatory response and the hereditary factors involved, thus increasing our understanding of the pathogenic mechanisms behind systemic vasculitis, 2. To use our knowledge of antigenic epitopes to increase the diagnostic yield from analysis of anti-GBM and ANCA, 3. To study different forms of therapy and thereby find treatments that will increase patient survival and reduce toxicity of treatment.
For patients with systemic vasculitis it is of major importance to be able to determine if the disease is active or not. Delay in treatment can rapidly lead to deterioration of vital organ functions, while institution of toxic immunosuppressive therapy for patients may have detrimental side effects, such as bladder cancer or serious infections. Targets for more specific therapy are therefore of vital significance. Systemic vasculitis can also be seen as a model for more common diseases, with slower progression rates. Knowledge of the pathogenesis of vasculitis can thus give important insights about other inflammatory diseases where autoimmune phenomenon are known to be of importance, such as chronic glomerulonephritis, rheumatoid arthritis and diabetes, as well as arteriosclerosis.
Link to project homepage: http://www.med.lu.se/klinvetlund/njurmedicin/systemiska_vaskuliter
5 recent original publications
Malin Carlsson, Swati Shukla, Ann Cathrine Petersson, Mårten Segelmark, and Thomas Hellmark
Pseudomonas aeruginosa in cystic fibrosis: pyocyanin negative strains are associated with BPI-ANCA and progressive lung disease.
J Cyst Fibros. 2011; 10: 265-271
M Abdgawad, L Gunnarsson, A A Bengtsson, P Geborek, L Nilsson, M Segelmark, and T Hellmark
Elevated neutrophil membrane expression of proteinase 3 is dependent upon CD177 expression.
Clin Exp Immunol. 2010; 161: 89-97
Susanne Bauer, Mohamed Abdgawad, Lena Gunnarsson, Mårten Segelmark, Hans Tapper, and Thomas Hellmark
Proteinase 3 and CD177 are expressed on the plasma membrane of the same subset of neutrophils.
J Leukoc Biol. 2007; 81: 458-464
T Hellmark, H Burkhardt, and J Wieslander
Goodpasture disease. Characterization of a single conformational epitope as the target of pathogenic autoantibodies.
J. Biol. Chem.. 1999; 274: 25862-25868
Thomas Hellmark, Lanlin Chen, Sophie Ohlsson, Jorgen Wieslander, and Warren Kline Bolton
Point mutations of single amino acids abolish ability of alpha3 NC1 domain to elicit experimental autoimmune glomerulonephritis in rats.
J. Biol. Chem.. 2003; 278: 46516-46522
Further publications here (new window)
|Total financing:||3.7 MSEK||Gov grant for clinical research ("ALF"):||1.3 MSEK|
|Total external financing:||2.3 MSEK||Natl and intl prioritized grants:||0.7 MSEK|