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PO10-TU-22 CSF proteome analysis in clinically isolated syndrome (CIS): candidate markers for conversion to definite multiple sclerosis
19th World Congress of Neurology, Poster Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S155–S339
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levels of IL-17 and IL-4 were not changed and not statistically different between two groups. Conclusions: TP is a potential agent to inhibit EAE effectively. Possible mechanism of TP may be related to suppression of MMP9, as well as downregulation of INF-? and upregulation of IL-10, which promote the deviation from Th1 cells to Th2 cells.
PO10-TU-23 Osteopontin plasma and cerebrospinal fluid evaluation in multiple sclerosis patients
PO10-TU-21 The predictive value of oligoclonal bands in the CSF for developing MS in ON: a complete literature survey
Purpose: Osteopontin (OPN), a pleiotropic cytokine with functions in cell-mediated immunity, inflammation, tissue repair, and cell survival, is highly overexpressed in Multiple sclerosis (MS) lesions. OPN has been found to be involved in leukocytes migration to the injured sites and to be synthesized by monocytes and macrophages within the injury sites. The exact role of OPN in the pathogenesis of MS is not completely understood. Our goal was to evaluate plasma and intrathecal production of OPN in early and late stages of MS course. Method: We analyzed 24 patients with clinically isolated syndrome (CIS), 15 patients with definite relapsing remitting (RR) MS and 18 healthy controls (HCs). Plasma and CSF samples of CIS and MS were collected simultaneously, aliquoted and stored immediately at −80ºC until use. OPN was measured in the plasma and cerebrospinal fluid (CSF) samples using commercially available ELISA kit. Intrathecal synthesis of OPN was calculated for each patients by OPN index (CSF:plasma OPN concentration/CSF:serum Albumin concentration). Results: Plasma OPN levels was significantly (p < 0.006) higher in CIS (80.3±27.3 ng/ml) than in RRMS (60.8±21.9 ng/ml) and HCs (55.2±12.6 ng/ml). OPN index resulted significantly (p = 0.026) higher in RRMS (0.76±0.34 ng/ml) than in CIS (0.55±0.44 ng/ml) patients and increased values were found during relapse in comparison to remission phases (p = 0.06). Intrathecal OPN synthesis correlated with IgG synthesis (p = 0.027), EDSS score (p = 0.018) and disease duration (p = 0.009). Conclusions: These data suggest a role of OPN both in early and late stages of MS: plasma OPN may provide to recruiting stimulus for leukocyte migration into central nervous system (CNS), whereas the intrathecal OPN production may be involved in the modulation of CNS inflammatory and tissue injury correlated with the disability progression of MS.
J.L. Frederiksen, A.G. Skov. Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark Purpose: Multiple sclerosis (MS) is an autoimmune disease of unknown aetiology, but it is generally accepted that genetic as well as environmental factors are important for the pathogenesis. Optic neuritis (ON) is often the first sign of MS, but it can be seen as an isolated symptom. It is important to predict which patients with ON will develop MS, especially because of the availability of immune modulating medicine. The aim of this study is to investigate the predictive value of oligoclonal bands (OB) in the prediction of patients at risk. Method: The study is a complete literature survey of the results of ten investigations localised by a search in PubMed. Results: Based on the available studies 19–67% of all patients with ON developed MS. OB as a predictive test has a sensitivity of 73– 100% (mean 89%) and a specificity of 41–90% (mean 57%). The OR-values are very variable between 2.75 and 171 (mean 34.2). Conclusions: OB is not a perfect predictive test but it contributes to the identification of the majority of the patients with ON who will develop MS. PO10-TU-22 CSF proteome analysis in clinically isolated syndrome (CIS): candidate markers for conversion to definite multiple sclerosis J. Brettschneider, V. Lehmensiek, V. Hirt, D. Rau, H. Tumani. University of Ulm, Ulm, Germany Purpose: In about 85% of patients who later develop MS, the disease initially presents with an acute or subacute episode of neurological symptoms due to a single demyelinating lesion, which is known as clinically isolated syndrome (CIS). Cerebrospinal fluid (CSF) is a promising source of biomarkers in CIS, since the CSF compartment is in close anatomical contact with the brain interstitial fluid, where biochemical changes related to the disease are reflected. Method: Using the two-dimensional difference in gel electrophoresis (2-D-DIGE), we compared CSF samples from patients with CIS that remained CIS (CIS-CIS, n = 8) over a follow-up time of 2 years and from patients with CIS that developed definite MS of the relapsing-remitting subtype (CIS-RRMS, n = 8) over the same period. Protein spots that showed significant differences between patients and controls were selected for further analysis by MALDI-TOF mass spectrometry. For validation of identified spots ELISA experiments were performed. Results: We identified 1 protein that was upregulated in CIS-RRMS (serin peptidase inhibitor) and 8 proteins (alpha-1-B-glycoprotein, Fetuin-A, apolipoprotein A4, haptoglobin, human Zinc-alpha-2glycoprotein (ZAG), Retinol-binding protein, superoxid dismutase 1, transferrin) that were down-regulated in CIS-RRMS vs. CIS-CIS. For Fetuin-A, our findings could be confirmed by ELISA. Conclusion: Our study provides new CSF candidate markers of disease progression to definite MS in patients with CIS. The pathophysiological role as well as clinical relevance of these candidate proteins in CIS remains to be further clarified by future studies.
M. Ruggieri, C. Pica, C. Tortorella, M. Mastrapasqua, R. Leante, D. Paolicelli, P. Iaffaldano, M. Trojano. Neurol. and Psych. Sciences Deptartment, University of Bari, Bari, Italy
PO10-TU-24 Study of the association between the human leukocyte antigen class I molecules and remitting relapsing multiple sclerosis (MS) D.O.A. Elsalamawy. Neurology, Faculty of Medicine, Alexandria, Egypt Objectives: The aim of this work is to study the frequencies of different HLA class I subtypes in Egyptian patients with remitting relapsing MS in order to find out genetic determinants to disease susceptibility among this genetic group. Methods: The study was carried out on twenty patients having Ms according to McDonald’s criteria, excluding those with clinical courses other than the remitting-relapsing one. All patients subjected to complete history taking, full physical and neurological examination, routine lab investigations, MRI of the brain and/or spinal cord, also HLA class I typing using the complement dependent microlymphocytotoxicity test. The result of HLA typing were compared to twenty healthy controls matched for age. Results: The study revealed the following results: • The most frequent HLA class I subtypes in our study group were: HLA-A1 (40%), A2 (30%), B7 (25%), A28 (15%), and Cw6 (15%). • Among those subtypes only HLA-B7 showed a statistically significant association with the MS patients suggesting a role of this HLA class I subtype in modulating susceptibility to the disease. • The HLA-Cw4 subtype showed a tendency toward an association with the control group approaching but not reaching a statistical significance suggesting a role of this subtype as a protective factor
S201
levels of IL-17 and IL-4 were not changed and not statistically different between two groups. Conclusions: TP is a potential agent to inhibit EAE effectively. Possible mechanism of TP may be related to suppression of MMP9, as well as downregulation of INF-? and upregulation of IL-10, which promote the deviation from Th1 cells to Th2 cells.
PO10-TU-23 Osteopontin plasma and cerebrospinal fluid evaluation in multiple sclerosis patients
PO10-TU-21 The predictive value of oligoclonal bands in the CSF for developing MS in ON: a complete literature survey
Purpose: Osteopontin (OPN), a pleiotropic cytokine with functions in cell-mediated immunity, inflammation, tissue repair, and cell survival, is highly overexpressed in Multiple sclerosis (MS) lesions. OPN has been found to be involved in leukocytes migration to the injured sites and to be synthesized by monocytes and macrophages within the injury sites. The exact role of OPN in the pathogenesis of MS is not completely understood. Our goal was to evaluate plasma and intrathecal production of OPN in early and late stages of MS course. Method: We analyzed 24 patients with clinically isolated syndrome (CIS), 15 patients with definite relapsing remitting (RR) MS and 18 healthy controls (HCs). Plasma and CSF samples of CIS and MS were collected simultaneously, aliquoted and stored immediately at −80ºC until use. OPN was measured in the plasma and cerebrospinal fluid (CSF) samples using commercially available ELISA kit. Intrathecal synthesis of OPN was calculated for each patients by OPN index (CSF:plasma OPN concentration/CSF:serum Albumin concentration). Results: Plasma OPN levels was significantly (p < 0.006) higher in CIS (80.3±27.3 ng/ml) than in RRMS (60.8±21.9 ng/ml) and HCs (55.2±12.6 ng/ml). OPN index resulted significantly (p = 0.026) higher in RRMS (0.76±0.34 ng/ml) than in CIS (0.55±0.44 ng/ml) patients and increased values were found during relapse in comparison to remission phases (p = 0.06). Intrathecal OPN synthesis correlated with IgG synthesis (p = 0.027), EDSS score (p = 0.018) and disease duration (p = 0.009). Conclusions: These data suggest a role of OPN both in early and late stages of MS: plasma OPN may provide to recruiting stimulus for leukocyte migration into central nervous system (CNS), whereas the intrathecal OPN production may be involved in the modulation of CNS inflammatory and tissue injury correlated with the disability progression of MS.
J.L. Frederiksen, A.G. Skov. Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark Purpose: Multiple sclerosis (MS) is an autoimmune disease of unknown aetiology, but it is generally accepted that genetic as well as environmental factors are important for the pathogenesis. Optic neuritis (ON) is often the first sign of MS, but it can be seen as an isolated symptom. It is important to predict which patients with ON will develop MS, especially because of the availability of immune modulating medicine. The aim of this study is to investigate the predictive value of oligoclonal bands (OB) in the prediction of patients at risk. Method: The study is a complete literature survey of the results of ten investigations localised by a search in PubMed. Results: Based on the available studies 19–67% of all patients with ON developed MS. OB as a predictive test has a sensitivity of 73– 100% (mean 89%) and a specificity of 41–90% (mean 57%). The OR-values are very variable between 2.75 and 171 (mean 34.2). Conclusions: OB is not a perfect predictive test but it contributes to the identification of the majority of the patients with ON who will develop MS. PO10-TU-22 CSF proteome analysis in clinically isolated syndrome (CIS): candidate markers for conversion to definite multiple sclerosis J. Brettschneider, V. Lehmensiek, V. Hirt, D. Rau, H. Tumani. University of Ulm, Ulm, Germany Purpose: In about 85% of patients who later develop MS, the disease initially presents with an acute or subacute episode of neurological symptoms due to a single demyelinating lesion, which is known as clinically isolated syndrome (CIS). Cerebrospinal fluid (CSF) is a promising source of biomarkers in CIS, since the CSF compartment is in close anatomical contact with the brain interstitial fluid, where biochemical changes related to the disease are reflected. Method: Using the two-dimensional difference in gel electrophoresis (2-D-DIGE), we compared CSF samples from patients with CIS that remained CIS (CIS-CIS, n = 8) over a follow-up time of 2 years and from patients with CIS that developed definite MS of the relapsing-remitting subtype (CIS-RRMS, n = 8) over the same period. Protein spots that showed significant differences between patients and controls were selected for further analysis by MALDI-TOF mass spectrometry. For validation of identified spots ELISA experiments were performed. Results: We identified 1 protein that was upregulated in CIS-RRMS (serin peptidase inhibitor) and 8 proteins (alpha-1-B-glycoprotein, Fetuin-A, apolipoprotein A4, haptoglobin, human Zinc-alpha-2glycoprotein (ZAG), Retinol-binding protein, superoxid dismutase 1, transferrin) that were down-regulated in CIS-RRMS vs. CIS-CIS. For Fetuin-A, our findings could be confirmed by ELISA. Conclusion: Our study provides new CSF candidate markers of disease progression to definite MS in patients with CIS. The pathophysiological role as well as clinical relevance of these candidate proteins in CIS remains to be further clarified by future studies.
M. Ruggieri, C. Pica, C. Tortorella, M. Mastrapasqua, R. Leante, D. Paolicelli, P. Iaffaldano, M. Trojano. Neurol. and Psych. Sciences Deptartment, University of Bari, Bari, Italy
PO10-TU-24 Study of the association between the human leukocyte antigen class I molecules and remitting relapsing multiple sclerosis (MS) D.O.A. Elsalamawy. Neurology, Faculty of Medicine, Alexandria, Egypt Objectives: The aim of this work is to study the frequencies of different HLA class I subtypes in Egyptian patients with remitting relapsing MS in order to find out genetic determinants to disease susceptibility among this genetic group. Methods: The study was carried out on twenty patients having Ms according to McDonald’s criteria, excluding those with clinical courses other than the remitting-relapsing one. All patients subjected to complete history taking, full physical and neurological examination, routine lab investigations, MRI of the brain and/or spinal cord, also HLA class I typing using the complement dependent microlymphocytotoxicity test. The result of HLA typing were compared to twenty healthy controls matched for age. Results: The study revealed the following results: • The most frequent HLA class I subtypes in our study group were: HLA-A1 (40%), A2 (30%), B7 (25%), A28 (15%), and Cw6 (15%). • Among those subtypes only HLA-B7 showed a statistically significant association with the MS patients suggesting a role of this HLA class I subtype in modulating susceptibility to the disease. • The HLA-Cw4 subtype showed a tendency toward an association with the control group approaching but not reaching a statistical significance suggesting a role of this subtype as a protective factor