Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Voortman, M.
Development of CSF and blood biomarkers in the clinical management of multiple sclerosis
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2023. pp. 129
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Archelos-Garcia Juan-Jose
- Khalil Michael
- Stojakovic Tatjana
- Altmetrics:
- Abstract:
- The overall aim of the work depicted in this dissertation was the analysis of biomarkers in CSF and blood of patients with early multiple sclerosis (MS) compared to controls, and evaluating their applicability in various clinical settings. Results on body fluid biomarkers were combined with longitudinal clinical and magnetic resonance imaging (MRI; at 3 T) patient data. Chapter 2 – We assessed the potential of free light chains kappa (KFLC) and lambda (LFCL) to serve as prognostic tool for disease progression in CSF and serum of 48/13 oligoclonal bands-positive patients with clinically isolated syndrome (CIS)/relapsing-remitting MS (RRMS) compared to 60 non-inflammatory neurological disease controls (NINDC). CSF parameters of both KFLC and LFLC were increased in diseased patients. CIS patients with a lower CSF KFLC/LFLC ratio had a 2.89-time higher risk to convert to clinically definite MS. Chapter 3 – Serum Netrin-1 (sNTN-1) was analysed in 31/48 CIS/RRMS and 30 NINDC to assess its potential to provide information on MS disease activity. No significant differences were found between patients and controls, or between patients with a gadolinium (Gd)-positive or -negative MRI. A small sub-group of Gd+ patients with simultaneous clinically active disease showed decreased sNTN-1 vs. clinically non-active Gd+ subjects. Chapter 4 – We compared antioxidative capacity (AOC) in CSF and blood, as measured fluorometrically, between 55/11 patients with CIS/RRMS and 67 NINDC. AOC in CSF was decreased in RRMS vs. CIS. Lower CSF AOC was in turn related to greater physical disability and increased risk for future relapses in MS. AOC did not correlate to MRI measures. Chapter 5 – FACS analysis of CD62L+ peripheral blood mononuclear cells in whole blood was performed within one hour upon sampling in 234 CIS/MS patients under various treatments and 51 healthy controls (HC). CD62L was decreased under natalizumab (NTZ) and fingolimod (FTY), and increased with dimethyl-fumarate when compared to interferon/glatiramer acetate, no treatment and HC. CD62L was stable over time with unchanged treatment, but was affected upon NTZ withdrawal or FTY introduction. Overall, we were able to show the potential clinical value of four body fluid biomarkers, each with a different supposed applicability. Next to their diagnostic potential, CSF KFLC and LFLC might aid in prognosticating disease activity. sNTN-1 cannot be used to detect radiological disease activity; nevertheless, it might serve a role in detecting MS pathology. AOC in CSF appears to play an important role in pathological processes related to oxidative stress, giving it potential as marker for disease activity or as treatment target itself. The direct FACS analysis of CD62L in fresh blood samples proofs the potential of the methodology and warrants further research on the potential of CD62L as marker in treatment response.