Active and Passive Immunization with Myelin Basic Protein as a Method for Early Treatment of Traumatic Spinal Cord Injury; a Meta-Analysis
Archives of Academic Emergency Medicine,
Vol. 9 No. 1 (2021),
1 Dey 2021
,
Page e57
https://doi.org/10.22037/aaem.v9i1.1316
Abstract
Introduction: Traumatic spinal cord injury (SCI), as a dangerous central nervous system damage, continues to threaten communities by imposing various disabilities and costs. Early adjustment of the immune system response using Myelin Basic Protein (MBP) immunization may prevent the SCI-related secondary damages. As a result, the current study is designed to review and analyse the evidence on active and passive immunization with MBP for treatment of traumatic SCI.
Methods: Medline, Embase, Scopus, and Web of Science databases were systematically searched until the end of 2020. Criteria for inclusion in the current study included pre-clinical studies, which performed passive (injection of MBP-activated T cells) or active (administration of MBP or MBP-modified peptides) immunization with MBP after traumatic SCI. Exclusion criteria was defined as lack of a non-treated SCI group, lack of evaluation of locomotion, review studies, and combination therapy. Finally, analyses were conducted using STATA software, and a standardized mean difference (SMD) with a 95% confidence interval (CI) were reported.
Results: Data from 17 papers were included in the present study. Finally, analysis of these data showed that passive immunization (SMD=0.87; 95%CI: 0.19-1.55; p=0.012) and active immunization (SMD=2.08, 95%CI: 1.42-2.73; p<0.001) for/with MBP both have good efficacy in improving locomotion following traumatic SCI. However, significant heterogeneity was observed in both of them. The most important sources of heterogeneity in active immunization were differences in SCI models, route of administration, time interval between SCI and transplantation, and type of vaccine used. In passive immunization, however, these sources were the model of SCI and the time interval between SCI and transplantation. Although, there was substantial heterogeneity among studies, subgroup analysis showed that active immunization improved locomotion after traumatic SCI in all tested conditions (with differences in injury model, severity of injury, method of administration, different time interval between SCI to vaccination, etc.).
Conclusion: The results of the present study demonstrated that immunization with MBP, especially in its active form, could significantly improve motor function following SCI in rats and mice. Therefore, it could be considered as a potential treatment in acute settings such as emergency departments. However, the safety of this method is still under debate. Therefore, it is recommended for future research to focus on the investigation of safety of MBP immunization in animal studies, before conducting human clinical trials.
- Early Medical Intervention
- Emergency treatment
- Immunization
- Myelin basic protein
- Spinal cord injuries
How to Cite
References
Mann R, Schaefer C, Sadosky A, Bergstrom F, Baik R, Parsons B, et al. Burden of spinal cord injury-related neuropathic pain in the United States: retrospective chart review and cross-sectional survey. Spinal cord. 2013;51(7):564-70.
Backonja MM, Irving GA, Argoff C. Rational multidrug therapy in the treatment of neuropathic pain. Curr Pain Headache Rep. 2006;10:34-8.
Marineo G, Iorno V, Gandini C, Moschini V, Smith TJ. Scrambler therapy may relieve chronic neuropathic pain more effectively than guideline-based drug management: Results of a pilot, randomized, controlled trial. Journal of pain and symptom management. 2012;43(1):87-95.
Hauben E, Butovsky O, Nevo U, Yoles E, Moalem G, Agranov E, et al. Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. The Journal of Neuroscience. 2000;20(17):6421-30.
Jones TB, Ankeny DP, Guan Z, McGaughy V, Fisher LC, Basso DM, et al. Passive or active immunization with myelin basic protein impairs neurological function and exacerbates neuropathology after spinal cord injury in rats. The Journal of neuroscience. 2004;24(15):3752-61.
Hausmann O. Post-traumatic inflammation following spinal cord injury. Spinal cord. 2003;41(7):369-78.
Brambilla R, Bracchi-Ricard V, Hu W-H, Frydel B, Bramwell A, Karmally S, et al. Inhibition of astroglial nuclear factor κB reduces inflammation and improves functional recovery after spinal cord injury. The Journal of experimental medicine. 2005;202(1):145-56.
Donnelly DJ, Popovich PG. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Experimental neurology. 2008;209(2):378-88.
Yoles E, Hauben E, Palgi O, Agranov E, Gothilf A, Cohen A, et al. Protective autoimmunity is a physiological response to CNS trauma. The Journal of Neuroscience. 2001;21(11):3740-8.
Moalem G, Leibowitz–Amit R, Yoles E, Mor F, Cohen IR, Schwartz M. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nature medicine. 1999;5(1):49-55.
Wang HJ, Hu JG, Shen L, Wang R, Wang QY, Zhang C, et al. Passive immunization with myelin basic protein activated T cells suppresses axonal dieback but does not promote axonal regeneration following spinal cord hemisection in adult rats. The International journal of neuroscience. 2012;122(8):458-65.
Wang Y, Li J, Kong P, Zhao S, Yang H, Chen C, et al. Enhanced expression of neurotrophic factors in the injured spinal cord through vaccination with myelin basic protein-derived peptide pulsed dendritic cells. Spine. 2015;40(2):95-101.
Liu H, Shiryaev SA, Chernov AV, Kim Y, Shubayev I, Remacle AG, et al. Immunodominant fragments of myelin basic protein initiate T cell-dependent pain. Journal of neuroinflammation. 2012;9:119.
Hauben E, Butovsky O, Nevo U, Yoles E, Moalem G, Agranov E, et al. Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2000;20(17):6421-30.
Ibarra A, Sosa M, García E, Flores A, Cruz Y, Mestre H, et al. Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured rats. Neuroscience letters. 2013;554:59-63.
Rodríguez-Barrera R, Fernández-Presas AM, García E, Flores-Romero A, Martiñón S, González-Puertos VY, et al. Immunization with a neural-derived peptide protects the spinal cord from apoptosis after traumatic injury. BioMed research international. 2013;2013:827517.
Rodríguez-Barrera R, Flores-Romero A, García E, Fernández-Presas AM, Incontri-Abraham D, Navarro-Torres L, et al. Immunization with neural-derived peptides increases neurogenesis in rats with chronic spinal cord injury. CNS Neuroscience and Therapeutics. 2020;26(6):650-8.
Ibarra A, Hauben E, Butovsky O, Schwartz M. The therapeutic window after spinal cord injury can accommodate T cell-based vaccination and methylprednisolone in rats. The European journal of neuroscience. 2004;19(11):2984-90.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Annals of internal medicine. 2009;151(4):264-9.
Sistrom CL, Mergo PJ. A simple method for obtaining original data from published graphs and plots. American Journal of Roentgenology. 2000;174(5):1241-4.
Hooijmans CR, Rovers MM, de Vries RBM, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. BMC Medical Research Methodology. 2014;14(1):43.
Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315(7109):629-34.
Hauben E, Gothilf A, Cohen A, Butovsky O, Nevo U, Smirnov I, et al. Vaccination with dendritic cells pulsed with peptides of myelin basic protein promotes functional recovery from spinal cord injury. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2003;23(25):8808-19.
Hu JG, Shen L, Wang R, Wang QY, Zhang C, Xi J, et al. Effects of Olig2-overexpressing neural stem cells and myelin basic protein-activated T cells on recovery from spinal cord injury. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2012;9(2):422-45.
Hu JG, Shi LL, Chen YJ, Xie XM, Zhang N, Zhu AY, et al. Differential effects of myelin basic protein-activated Th1 and Th2 cells on the local immune microenvironment of injured spinal cord. Exp Neurol. 2016;277:190-201.
Liu M, Zhao J, Liang H, Bian X. Vaccination with dendritic cells pulsed with homogenate protein of spinal cord promotes functional recovery from spinal cord injury in mice. Spinal cord. 2009;47(5):360-6.
Lü HZ, Xu L, Zou J, Wang YX, Ma ZW, Xu XM, et al. Effects of autoimmunity on recovery of function in adult rats following spinal cord injury. Brain, behavior, and immunity. 2008;22(8):1217-30.
Martiñon S, García E, Flores N, Gonzalez I, Ortega T, Buenrostro M, et al. Vaccination with a neural-derived peptide plus administration of glutathione improves the performance of paraplegic rats. The European journal of neuroscience. 2007;26(2):403-12.
Martiñón S, García E, Gutierrez-Ospina G, Mestre H, Ibarra A. Development of protective autoimmunity by immunization with a neural-derived peptide is ineffective in severe spinal cord injury. PloS one. 2012;7(2):e32027.
Martiñón S, García-Vences E, Toscano-Tejeida D, Flores-Romero A, Rodriguez-Barrera R, Ferrusquia M, et al. Long-term production of BDNF and NT-3 induced by A91-immunization after spinal cord injury. BMC neuroscience. 2016;17(1):42.
Schwartz M, Raposo C. Protective autoimmunity: a unifying model for the immune network involved in CNS repair. The Neuroscientist. 2014;20(4):343-58.
Held W, Meyermann R, Qin Y, Mueller C. Perforin and tumor necrosis factor α in the pathogenesis of experimental allergic encephalomyelitis: comparison of autoantigen induced and transferred disease in Lewis rats. Journal of autoimmunity. 1993;6(3):311-22.
Zang YC, Li S, Rivera VM, Hong J, Robinson RR, Breitbach WT, et al. Increased CD8+ cytotoxic T cell responses to myelin basic protein in multiple sclerosis. The Journal of Immunology. 2004;172(8):5120-7.
Zhang J, Medaer R, Stinissen P, Hafler D, Raus J. MHC-restricted depletion of human myelin basic protein-reactive T cells by T cell vaccination. Science. 1993;261(5127):1451-4.
- Abstract Viewed: 1558 times
- pdf Downloaded: 531 times
