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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Chief Physician Kristofer Andréasson, Lund University, Sweden
- Second opponent: Associate Professor Gro Østli Eilertsen, UiT - The Arctic University of Norway
- Third member and chair of the evaluation committee: Professor II Hilde Berner Hammer, University of Oslo
Chair of the Defence
Associate Professor Silje Watterdal Syversen, University of Oslo
Principal Supervisor
Professor Øyvind Molberg, University of Oslo
Summary
Systemic sclerosis (SSc) is a disease leading to fibrosis of skin and organs, vasculopathy and autoimmune features. One of the most common causes of death in SSc in pulmonary arterial hypertension (PAH). Early diagnosis of PAH are crucial, and the need for early detection biomarkers are high. Another serious condition in SSc is affliction of the gastro intestinal tract (GIT). The mechanism behind GIT complications is unclear, and treatment options are limited. A recent pilot study on fecal microbiota transplantation (FMT) in SSc patients indicated effects on lower GIT symptoms, but the mechanisms behind are unknown.
The aim of this study was to identify and investigate biomarkers for PAH and GIT involvement in SSc. We included SSc patients from Oslo, Zurich and Los Angeles, and used immune assays to analyze the levels of the lymphangiogenic factors VEGF-C, Ang-2, their receptors VEGFR3 and Tie-2, and CCL21 in serum samples to investigate their ability as predictive markers for PAH. We also investigated the effect of FMT on inflammatory, fibrotic and lymphaniogenic factors in the duodenum of SSc patients by immunohistochemistry and transcriptome profiling.
We found that serum levels of VEGF-C were lower in SSc compared to healthy controls, and VEGF-C and sVEGFR3 were associated with the development of PAH. Serum levels of CCL21 were higher in SSc patients, especially the once with PAH. In the analysis of the duodenal tissue samples, we found reduced expression of the factors podoplanin and CD64, which correlated with reduced GIT-symptoms. We also found a change in the expression of genes associated with important biological processes after treatment with FMT.
Overall, we identified novel potential biomarkers for the development of PAH in SSc, and showed that FMT may change the expression of genes related to inflammation, fibrosis and lymphaniogenesis in the duodenum. These results gives hope for new diagnostic tools and therapy methods in SSc.
Additional information
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