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以髓鞘碱性蛋白进行主动和被动免疫作为创伤性脊髓损伤早期治疗方法的荟萃分析

Active and Passive Immunization with Myelin Basic Protein as a Method for Early Treatment of Traumatic Spinal Cord Injury; a Meta-Analysis.

作者信息

Yousefifard Mahmoud, Madani Neishaboori Arian, Rafiei Alavi Seyedeh Niloufar, Toloui Amirmohammad, Gubari Mohammed I M, Zareie Shab Khaneh Amirali, Karimi Ghahfarokhi Maryam, Hosseini Mostafa

机构信息

Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.

First and second authors have equally contributed to this work.

出版信息

Arch Acad Emerg Med. 2021 Aug 30;9(1):e57. doi: 10.22037/aaem.v9i1.1316. eCollection 2021.

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.

摘要

引言

创伤性脊髓损伤(SCI)作为一种危险的中枢神经系统损伤,通过造成各种残疾和带来高昂成本,持续威胁着社会。使用髓鞘碱性蛋白(MBP)免疫早期调节免疫系统反应可能预防与SCI相关的继发性损伤。因此,本研究旨在回顾和分析有关用MBP进行主动和被动免疫治疗创伤性SCI的证据。

方法

系统检索了Medline、Embase、Scopus和Web of Science数据库直至2020年底。纳入本研究的标准包括临床前研究,这些研究在创伤性SCI后进行了被动(注射MBP激活的T细胞)或主动(给予MBP或MBP修饰的肽)MBP免疫。排除标准定义为缺乏未治疗的SCI组、缺乏运动评估、综述研究和联合治疗。最后,使用STATA软件进行分析,并报告标准化平均差(SMD)及95%置信区间(CI)。

结果

本研究纳入了17篇论文的数据。最后,对这些数据的分析表明,MBP的被动免疫(SMD = 0.87;95%CI:0.19 - 1.55;p = 0.012)和主动免疫(SMD = 2.08,95%CI:1.42 - 2.73;p < 0.001)在改善创伤性SCI后的运动功能方面均具有良好疗效。然而,两者均观察到显著的异质性。主动免疫中异质性的最重要来源是SCI模型、给药途径、SCI与移植之间的时间间隔以及所用疫苗的类型。而在被动免疫中,这些来源是SCI模型以及SCI与移植之间 的时间间隔。尽管研究间存在很大异质性,但亚组分析表明,在所有测试条件下(损伤模型、损伤严重程度、给药方法、SCI至接种疫苗的不同时间间隔等存在差异),主动免疫均能改善创伤性SCI后的运动功能。

结论

本研究结果表明,用MBP免疫,尤其是其主动形式,可显著改善大鼠和小鼠SCI后的运动功能。因此,在急诊科等急性情况下,它可被视为一种潜在的治疗方法。然而,该方法的安全性仍存在争议。因此,建议未来研究在进行人体临床试验之前,重点关注动物研究中MBP免疫安全性的调查。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fdb/8464018/8df3a21406f2/aaem-9-e57-g001.jpg

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