Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Seifried, K.
Redox state of human serum albumin in serum and cerebrospinal fluid of patients with multiple sclerosis
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2024. pp. 84
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Khalil Michael
- Öttl Karl
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- Abstract:
- Background and aim As in many other pathologies, including neurodegenerative diseases, oxidative stress has been shown to play a role in the pathophysiology of multiple sclerosis (MS). Human serum albumin (HSA) is the most abundant protein in blood and various other body fluids, such as cerebrospinal fluid (CSF). According to its redox state in terms of cysteine-34 (Cys-34), HSA can serve as an indicator of oxidative stress. In this diploma thesis, we aimed to analyze the redox state of HSA in serum and CSF of MS patients in comparison to controls, and to further determine potential associations with disease activity and severity. This should serve as a pilot study in the search for MS biomarkers. Methods We performed high performance liquid chromatography (HPLC) on paired serum and CSF samples of 20 MS patients and 21 symptomatic controls, to determine the percentual allocation of HSA to the fractions human mercaptalbumin (HMA), human non-mercaptalbumin 1 (HNA1) and human non-mercaptalbumin 2 (HNA2). HMA is the reduced form of the protein, with a free thiol group on Cys-34. In HNA1, HSA is reversibly oxidized with Cys-34 as disulfide together with another thiol, whereas HNA2 is irreversibly oxidized with Cys-34 as sulfinic or sulfonic acid. We then tested for differences in HSA fraction allocation between groups and between serum and CSF, as well as for associations of HSA redox status with disease parameters reflecting activity and severity. Results We did not find an overall significant difference in HSA redox state between MS patients and controls, although CSF HNA2 showed a trend to higher fractions. In CSF, HMA fractions were significantly higher than in serum, while HNA1 and HNA2 fractions were lower. We found significant associations of albumin redox state in serum with physical disability in remission in MS patients, as well as significant associations of albumin redox state in CSF and serum and disease activity. Additionally, there were some significant correlations of HSA redox state in both compartments with age, as well as significant correlations of HSA fraction allocation in serum with lactate in CSF. Conclusion In conclusion, our data affirm the involvement of oxidative stress in MS pathophysiology. This study should serve as a basis for further investigation of HSA in MS, particularly in larger cohorts and patients with more advanced disease stages. In addition, our findings contribute to comprehension of the redox environment in CSF, and propose HSA as an interesting analyte for further research in this still poorly understood area.