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Schmidt, Katrin (2010)
Publisher: Freie Universität Berlin Universitätsbibliothek, Garystr. 39, 14195 Berlin
Languages: German
Types: Doctoral thesis
Subjects: 610 Medizin und Gesundheit, 610 Medical sciences; Medicine
ddc: ddc:610

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mesheuropmc: respiratory system, respiratory tract diseases
Systemic sclerosis (SSc) is a rare connective tissue disease characterized by increased production of extracellular matrix, endothelial dysfunction and immunity abnormalities. SSc is considered as a devastating multiorgan disease of unknown etiology with an autoimmunological background. In the present work we have measured levels of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) and serum in cohorts of Ssc-patients, patients with other lung diseases and healthy donors. We have analyzed differences in order to identify key cytokines specifically involved in the pathogenesis of Ssc-related lung disease. Furthermore, correlation of cytokine and chemokine levels with clinical parameters, especially with signs of lung fibrosis was studied. Additionally we have analyzed the predictive value of cytokines by follow-up investigations. The present study identified several abnormalities in the cytokine and chemokine networks in BALF and serum of Ssc-patients. We have recognized key cytokines for example MCP-1 an IL-8, which were associated with lung fibrosis and able to predict worsening of interstitial lung disease in Ssc-patients. Beyond that we found an association between cytokine levels and lung function parameters. Most convincing and not previously shown, high cytokine levels in BALF together with high levels of Anti-AT1-receptor-Antibodies (Anti-AT1-R-Ab) respectively Anti-ETA-receptor-Antibodies (Anti-ETA-R-Ab) were associated with worsening of interstitial lung disease (ILD) and the development of endstage ILD. For this reason levels of BALF cytokines achieve prognostic importance and BALF gets clinical impact beyond the diagnosis of specific lung disease. According to our results, MCP-1 and probably IL-8 and Anti-AT1-R-Ab respectively Anti-ETA-R-Ab appear to be the most promising candidate for a targeted therapy in systemic sclerosis. These cytokines may be perspectively established as marker for diagnosis, progression and prediction.
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