Contributions
Abstract: P644
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Introduction: Oxidative stress (OS) is a major feature of multiple sclerosis (MS) and promotes damage to proteins, lipids and DNA, and finally neuronal death. OS induced toxic effects may be limited by the antioxidative capacity (AOC) in body fluids, which acts as an important defence mechanism. An imbalance of OS and AOC may therefore facilitate tissue damage in MS. Various reactive oxidative species have been investigated so far; however, the relation of AOC in body fluids to clinical outcome measures in MS remains inconclusive.
Objective: To compare AOC in serum and cerebrospinal fluid (CSF) between MS patients and controls, and assess its relation with clinical measures in MS.
Methods: We included patients with a clinically isolated syndrome (CIS) or MS (n=57/13; 68.6% female; age median 32.3, IQR 26.6-40.0 years; disease duration median 0.5, IQR 0.3-4.9 months; Expanded Disability Status Scale (EDSS) score median 1.5, IQR 0.0-3.0) and controls with other non-inflammatory neurological diseases (n=67; 67.2% female; age median 32.7, IQR 25.2-44.9 years). All subjects underwent diagnostic CSF and serum sampling. AOC was determined for all CSF/serum samples as the sample's ability to inhibit 2,2´-azobis(2-amidinopropane) dihydrochloride (AAPH) induced oxidation of dihydrorhodamine (DHR). Clinical follow-up was available in all patients (time period median 3.1, IQR 1.4-4.8 years).
Results: In general, AOC did not differ between CIS/MS patients (median 46.3, IQR 41.3-49.9 %; median 29.5, IQR 19.6-40.8 %) and controls (median 47.0, IQR 430-50.0 %; median 32.8, IQR 23.0-41.4 %) for both serum and CSF, respectively. However, we found lower CSF AOC in patients with active disease (clinical relapse within 30 days prior to sampling, n=46) compared to non-active disease or controls (both p=0.03), and in patients with higher EDSS (≥3, n=19) vs. EDSS < 3 (p=0.001) or controls (p=0.01). CSF AOC was further negatively correlated with EDSS at time of sampling (clinically active (r=-0.4, p=0.003) and non-active patients (r=-0.6, p=0.001)). CIS patients who later converted to clinically definite MS (n=16) had lower CSF AOC compared to non-converters (n=41) (p=0.01).
Conclusion: Decreased CSF AOC is associated with disease activity and progression in MS patients. The AOC thus seems to be a critical factor to counteract MS pathology. Further research is warranted to investigate the potential role of AOC as a treatment target in MS.
Disclosure: This study was supported by ministerial funding of the Austrian Federal Ministry of Economics and Research.
- Ms Voortman received funding from the Austrian Federal Ministry of Science, Research and Economics and was trained within the frame of the PhD Program Molecular Medicine of the Medical University of Graz.
- Dr. Pichler: nothing to disclose.
- Dr. Enzinger has received funding for travel and speaker honoraria from Biogen Idec, Bayer Schering Pharma, Merck Serono, Shire, Novartis Genzyme and Teva Pharmaceutical Industries Ltd./sanofi-aventis; research support from Merck Serono, Biogen Idec., and Teva Pharmaceutical Industries Ltd./sanofi-aventis; is serving on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva Pharmaceutical Industries Ltd./sanofiaventis; and has acted as academic editor for PLOSOne.
- Dr. Fuchs serves on scientific advisory boards and / or has received speaker honoraria from Biogen Idec, Novartis, Genzyme, Merck, Roche and TEVA Pharmaceutical Industries.
- Dr. Bachmaier: nothing to disclose.
- Dr. Archelos: nothing to disclose.
- Dr. Fazekas serves on scientific advisory boards for Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and Teva Pharmaceutical Industries Ltd.; serves on the editorial boards of Multiple Sclerosis, the Polish Journal of Neurology and Neurosurgery, and the Swiss Archives of Neurology and Psychiatry; provides services for Actelion and Parexel and has received speaker honoraria and support from Almirall, Merck Serono, Novartis, Pfizer, Roche, Shire and Teva Pharmaceutical Industries Ltd.
- Dr. Marsche: nothing to disclose.
- Dr. Khalil has received funding for travel and speaker honoraria from Bayer Schering Pharma, Novartis Genzyme, Merck Serono, Biogen Idec and Teva Pharmaceutical Industries.
Abstract: P644
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Introduction: Oxidative stress (OS) is a major feature of multiple sclerosis (MS) and promotes damage to proteins, lipids and DNA, and finally neuronal death. OS induced toxic effects may be limited by the antioxidative capacity (AOC) in body fluids, which acts as an important defence mechanism. An imbalance of OS and AOC may therefore facilitate tissue damage in MS. Various reactive oxidative species have been investigated so far; however, the relation of AOC in body fluids to clinical outcome measures in MS remains inconclusive.
Objective: To compare AOC in serum and cerebrospinal fluid (CSF) between MS patients and controls, and assess its relation with clinical measures in MS.
Methods: We included patients with a clinically isolated syndrome (CIS) or MS (n=57/13; 68.6% female; age median 32.3, IQR 26.6-40.0 years; disease duration median 0.5, IQR 0.3-4.9 months; Expanded Disability Status Scale (EDSS) score median 1.5, IQR 0.0-3.0) and controls with other non-inflammatory neurological diseases (n=67; 67.2% female; age median 32.7, IQR 25.2-44.9 years). All subjects underwent diagnostic CSF and serum sampling. AOC was determined for all CSF/serum samples as the sample's ability to inhibit 2,2´-azobis(2-amidinopropane) dihydrochloride (AAPH) induced oxidation of dihydrorhodamine (DHR). Clinical follow-up was available in all patients (time period median 3.1, IQR 1.4-4.8 years).
Results: In general, AOC did not differ between CIS/MS patients (median 46.3, IQR 41.3-49.9 %; median 29.5, IQR 19.6-40.8 %) and controls (median 47.0, IQR 430-50.0 %; median 32.8, IQR 23.0-41.4 %) for both serum and CSF, respectively. However, we found lower CSF AOC in patients with active disease (clinical relapse within 30 days prior to sampling, n=46) compared to non-active disease or controls (both p=0.03), and in patients with higher EDSS (≥3, n=19) vs. EDSS < 3 (p=0.001) or controls (p=0.01). CSF AOC was further negatively correlated with EDSS at time of sampling (clinically active (r=-0.4, p=0.003) and non-active patients (r=-0.6, p=0.001)). CIS patients who later converted to clinically definite MS (n=16) had lower CSF AOC compared to non-converters (n=41) (p=0.01).
Conclusion: Decreased CSF AOC is associated with disease activity and progression in MS patients. The AOC thus seems to be a critical factor to counteract MS pathology. Further research is warranted to investigate the potential role of AOC as a treatment target in MS.
Disclosure: This study was supported by ministerial funding of the Austrian Federal Ministry of Economics and Research.
- Ms Voortman received funding from the Austrian Federal Ministry of Science, Research and Economics and was trained within the frame of the PhD Program Molecular Medicine of the Medical University of Graz.
- Dr. Pichler: nothing to disclose.
- Dr. Enzinger has received funding for travel and speaker honoraria from Biogen Idec, Bayer Schering Pharma, Merck Serono, Shire, Novartis Genzyme and Teva Pharmaceutical Industries Ltd./sanofi-aventis; research support from Merck Serono, Biogen Idec., and Teva Pharmaceutical Industries Ltd./sanofi-aventis; is serving on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva Pharmaceutical Industries Ltd./sanofiaventis; and has acted as academic editor for PLOSOne.
- Dr. Fuchs serves on scientific advisory boards and / or has received speaker honoraria from Biogen Idec, Novartis, Genzyme, Merck, Roche and TEVA Pharmaceutical Industries.
- Dr. Bachmaier: nothing to disclose.
- Dr. Archelos: nothing to disclose.
- Dr. Fazekas serves on scientific advisory boards for Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and Teva Pharmaceutical Industries Ltd.; serves on the editorial boards of Multiple Sclerosis, the Polish Journal of Neurology and Neurosurgery, and the Swiss Archives of Neurology and Psychiatry; provides services for Actelion and Parexel and has received speaker honoraria and support from Almirall, Merck Serono, Novartis, Pfizer, Roche, Shire and Teva Pharmaceutical Industries Ltd.
- Dr. Marsche: nothing to disclose.
- Dr. Khalil has received funding for travel and speaker honoraria from Bayer Schering Pharma, Novartis Genzyme, Merck Serono, Biogen Idec and Teva Pharmaceutical Industries.