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Microrna regulation of B cells in multiple sclerosis: MIR-320 and its specific targets
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Abstracts / Journal of the Neurological Sciences 333 (2013) e358–e421
decreased QoL was associated with higher BDI scores (p b 0.001). Longterm disease duration was associated with lower QoL. Decrease of QoL was directly proportional to the high degree of neurological deficit and frequency of new attacks. Conclusion: Decreased QoL is primarily connected with long-term disease duration, degree of neurological deficit, frequency of new attacks and depth of depression. QoL must be considered in effective management of MS patients. doi:10.1016/j.jns.2013.07.1337
Abstract — WCN 2013 No: 2770 Topic: 6 — MS & Demyelinating Diseases Carbonyl proteins as marker of oxidative stress derived protein damage in neuroinflammatory and neurodegenerative diseases P. Rommera, J. Greilbergerb, R. Herwigc, E. Auffa, F. Leutmezera. a Neurology, Medical University of Vienna, Vienna, Austria; bPhysiology, Medical University Graz, Graz, Austria; cUrology, Medical University of Vienna, Vienna, Austria Background: The importance of oxidative stress in the genesis of neuro-immunological diseases has been discussed extensively. Carbonyl groups may be the end link of a series of metabolic processes leading to apoptosis and neuron damage. Multiple sclerosis (MS) is the most common chronic neuro-inflammatory disease and a major cause for disability in young adults. Oxidative stress is driven by inflammation and leads to degeneration. By now, established markers of oxidative stress in CSF are rare. The aim of the study is to detect carbonyl proteins in CSF in patients with MS, neurodegenerative diseases and healthy controls. Materials and methods: CSF from diagnostic lumbar punctures was tested. To determine levels of oxidative stress in cerebrospinal fluid (CSF) Carbonyl Protein was measured by the Carbonyl Protein ELISA Kit (Immundiagnostik AG, Germany). Results: Patients were divided in three subgroups (neuro-immunological disease, neurodegenerative disease, healthy controls). Level of CP differed significantly between subgroups (p = 0.025) (Kruskal–Wallis-Test), mean values: neuro-immunological disease 630.8, neurodegenerative disease 756.1, and healthy controls 356.5. Conclusion: In this pilot trial we tried to detect carbonyl groups (proteins?) as markers of oxidative stress. The results of this trial showed a significant difference in the mean levels of proteins in CDMS and neurodegenerative diseases in comparison to healthy controls. In conclusion, the trial showed that carbonyl proteins are able to serve as marker for oxidative stress. Larger trials have to show whether carbonyl proteins may be able to serve as biomarker for more severe course of disease or for developing CDMS in patients with CIS. doi:10.1016/j.jns.2013.07.1338
Abstract — WCN 2013 No: 2771 Topic: 6 — MS & Demyelinating Diseases NK cell expansion predicts treatment response to rituximab P.S. Rommer, E. Auff, F. Leutmezer. Neurology, Medical University of Vienna, Vienna, Austria Background: Rituximab is used in a plenty of neuro-immunological diseases although it has not been approved for any neurological disease. Positive results have been published for relapsing–remitting Multiple Sclerosis (RRMS), Neuromyelitis optica (NMO) as well as case reports on
secondary progressive MS (SPMS), and myasthenia gravis (MG). Results in RRMS and NMO are impressive, whereas results are inconsistently in progressive MS and MG. Because of possible side effects of rituximab, biomarkers to predict clinical response to rituximab would be of particular interest. In rheumatoid arthritis, a favourable response to CD20 therapeutics was associated with an increase in NK. The aim of this study was to detect predictors of efficacy in patients with neuroinflammatory diseases treated with rituximab. Methods: We determined the levels of CD3+, CD3+CD8+, CD3+HLADR+, CD3−CD16&56+ and CD3+CD16&56 + cells in patients with neuro-immunological diseases. Results: Overall fourteen patients were included in this study. Patients were grouped in responders and non-responders according to clinical disease progression during rituximab therapy. Responders showed a higher ß and R2 for NK-cells in contrast to non-responders. The difference between these groups differed significantly (p b 0.001). Conclusion: We found a statistically significant difference between responders and non-responders to Rituximab therapy in patients with neuro-immunological diseases. Responders showed a higher increase in the NK-cell population following initiation of Rituximab treatment as compared to non-responders. Our results are in line with those in rheumatoid arthritis. Therefore we suggest that NK-cells might serve as a predictor of clinically favourable treatment response to Rituximab in patients with neuroinflammatory diseases. doi:10.1016/j.jns.2013.07.1339
Abstract — WCN 2013 No: 2774 Topic: 6 — MS & Demyelinating Diseases Microrna regulation of B cells in multiple sclerosis: MIR-320 and its specific targets L.L. Aung, S. Dhib-Jalbut, K.E. Balashov. Neurology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA Background and objective: B cells are strongly implicated in the pathogenesis of multiple sclerosis (MS). The role of microRNA (miRNA) in MS is not well understood. We studied if miRNAs regulate pro-inflammatory capabilities of B cells in MS. Patients and methods: B cells and monocytes were separated from untreated patients with MS and age- and gender-matched control healthy subjects (CHS). Expression of 904 miRNAs was tested by microarrays followed by validation with real-time qPCR. Expression of molecules targeted by miRNAs was analyzed by Western blot, ELISA and Flow cytometry. Transfection experiments with miRNA inhibitors were conducted to prove the inhibitory effect of endogenous miRNAs on expression of its targets. Results: Expression of miR-320 was significantly decreased in B cells of MS patients compared to CHS, p = 0.014, but not in monocytes. Expression of molecules specifically targeted by miR-320, Matrix metallopeptidase 9 (MMP-9), the protein implicated in disruption of blood-brain barrier, and Transferrin receptor protein 1 (TFRC), was significantly increased in B cells of patients. To test whether endogenous miRNA-320 inhibits MMP-9 secretion and TFRC expression, B cells from CHS were transfected with specific miR-320 inhibitor which led to increased TFRC expression and MMP-9 secretion to levels seen in patients with MS. Conclusion: miR-320 expression is selectively decreased in B cells of patients with MS. This is associated with increased expression of miR-320-specific targets, TFRC and MMP-9, which promote cell proliferation and blood–brain barrier disruption, respectively. doi:10.1016/j.jns.2013.07.1340
Abstracts / Journal of the Neurological Sciences 333 (2013) e358–e421
decreased QoL was associated with higher BDI scores (p b 0.001). Longterm disease duration was associated with lower QoL. Decrease of QoL was directly proportional to the high degree of neurological deficit and frequency of new attacks. Conclusion: Decreased QoL is primarily connected with long-term disease duration, degree of neurological deficit, frequency of new attacks and depth of depression. QoL must be considered in effective management of MS patients. doi:10.1016/j.jns.2013.07.1337
Abstract — WCN 2013 No: 2770 Topic: 6 — MS & Demyelinating Diseases Carbonyl proteins as marker of oxidative stress derived protein damage in neuroinflammatory and neurodegenerative diseases P. Rommera, J. Greilbergerb, R. Herwigc, E. Auffa, F. Leutmezera. a Neurology, Medical University of Vienna, Vienna, Austria; bPhysiology, Medical University Graz, Graz, Austria; cUrology, Medical University of Vienna, Vienna, Austria Background: The importance of oxidative stress in the genesis of neuro-immunological diseases has been discussed extensively. Carbonyl groups may be the end link of a series of metabolic processes leading to apoptosis and neuron damage. Multiple sclerosis (MS) is the most common chronic neuro-inflammatory disease and a major cause for disability in young adults. Oxidative stress is driven by inflammation and leads to degeneration. By now, established markers of oxidative stress in CSF are rare. The aim of the study is to detect carbonyl proteins in CSF in patients with MS, neurodegenerative diseases and healthy controls. Materials and methods: CSF from diagnostic lumbar punctures was tested. To determine levels of oxidative stress in cerebrospinal fluid (CSF) Carbonyl Protein was measured by the Carbonyl Protein ELISA Kit (Immundiagnostik AG, Germany). Results: Patients were divided in three subgroups (neuro-immunological disease, neurodegenerative disease, healthy controls). Level of CP differed significantly between subgroups (p = 0.025) (Kruskal–Wallis-Test), mean values: neuro-immunological disease 630.8, neurodegenerative disease 756.1, and healthy controls 356.5. Conclusion: In this pilot trial we tried to detect carbonyl groups (proteins?) as markers of oxidative stress. The results of this trial showed a significant difference in the mean levels of proteins in CDMS and neurodegenerative diseases in comparison to healthy controls. In conclusion, the trial showed that carbonyl proteins are able to serve as marker for oxidative stress. Larger trials have to show whether carbonyl proteins may be able to serve as biomarker for more severe course of disease or for developing CDMS in patients with CIS. doi:10.1016/j.jns.2013.07.1338
Abstract — WCN 2013 No: 2771 Topic: 6 — MS & Demyelinating Diseases NK cell expansion predicts treatment response to rituximab P.S. Rommer, E. Auff, F. Leutmezer. Neurology, Medical University of Vienna, Vienna, Austria Background: Rituximab is used in a plenty of neuro-immunological diseases although it has not been approved for any neurological disease. Positive results have been published for relapsing–remitting Multiple Sclerosis (RRMS), Neuromyelitis optica (NMO) as well as case reports on
secondary progressive MS (SPMS), and myasthenia gravis (MG). Results in RRMS and NMO are impressive, whereas results are inconsistently in progressive MS and MG. Because of possible side effects of rituximab, biomarkers to predict clinical response to rituximab would be of particular interest. In rheumatoid arthritis, a favourable response to CD20 therapeutics was associated with an increase in NK. The aim of this study was to detect predictors of efficacy in patients with neuroinflammatory diseases treated with rituximab. Methods: We determined the levels of CD3+, CD3+CD8+, CD3+HLADR+, CD3−CD16&56+ and CD3+CD16&56 + cells in patients with neuro-immunological diseases. Results: Overall fourteen patients were included in this study. Patients were grouped in responders and non-responders according to clinical disease progression during rituximab therapy. Responders showed a higher ß and R2 for NK-cells in contrast to non-responders. The difference between these groups differed significantly (p b 0.001). Conclusion: We found a statistically significant difference between responders and non-responders to Rituximab therapy in patients with neuro-immunological diseases. Responders showed a higher increase in the NK-cell population following initiation of Rituximab treatment as compared to non-responders. Our results are in line with those in rheumatoid arthritis. Therefore we suggest that NK-cells might serve as a predictor of clinically favourable treatment response to Rituximab in patients with neuroinflammatory diseases. doi:10.1016/j.jns.2013.07.1339
Abstract — WCN 2013 No: 2774 Topic: 6 — MS & Demyelinating Diseases Microrna regulation of B cells in multiple sclerosis: MIR-320 and its specific targets L.L. Aung, S. Dhib-Jalbut, K.E. Balashov. Neurology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA Background and objective: B cells are strongly implicated in the pathogenesis of multiple sclerosis (MS). The role of microRNA (miRNA) in MS is not well understood. We studied if miRNAs regulate pro-inflammatory capabilities of B cells in MS. Patients and methods: B cells and monocytes were separated from untreated patients with MS and age- and gender-matched control healthy subjects (CHS). Expression of 904 miRNAs was tested by microarrays followed by validation with real-time qPCR. Expression of molecules targeted by miRNAs was analyzed by Western blot, ELISA and Flow cytometry. Transfection experiments with miRNA inhibitors were conducted to prove the inhibitory effect of endogenous miRNAs on expression of its targets. Results: Expression of miR-320 was significantly decreased in B cells of MS patients compared to CHS, p = 0.014, but not in monocytes. Expression of molecules specifically targeted by miR-320, Matrix metallopeptidase 9 (MMP-9), the protein implicated in disruption of blood-brain barrier, and Transferrin receptor protein 1 (TFRC), was significantly increased in B cells of patients. To test whether endogenous miRNA-320 inhibits MMP-9 secretion and TFRC expression, B cells from CHS were transfected with specific miR-320 inhibitor which led to increased TFRC expression and MMP-9 secretion to levels seen in patients with MS. Conclusion: miR-320 expression is selectively decreased in B cells of patients with MS. This is associated with increased expression of miR-320-specific targets, TFRC and MMP-9, which promote cell proliferation and blood–brain barrier disruption, respectively. doi:10.1016/j.jns.2013.07.1340