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一种单克隆天然自身抗体在多发性硬化症小鼠模型中促进髓鞘再生的多器官反应性。

Multi-organ reactivity of a monoclonal natural autoantibody that promotes remyelination in a mouse model of multiple sclerosis.

作者信息

Miller D J, Njenga M K, Parisi J E, Rodriguez M

机构信息

Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota, USA.

出版信息

J Histochem Cytochem. 1996 Sep;44(9):1005-11. doi: 10.1177/44.9.8773566.

DOI:10.1177/44.9.8773566
PMID:8773566
Abstract

A contemporary view of autoimmunity suggests that self-reactivity is a normal phenomenon, in contrast to the classical association between autoimmunity and immunopathology. We have previously demonstrated that monoclonal antibody SCH94.03, a natural autoantibody with polyreactivity towards several purified protein and hapten antigens, promotes central nervous system remyelination when passively transferred to SJL/J mice chronically infected with Theiler's murine encephalomyelitis virus, an established experimental model of multiple sclerosis. In this study we characterized the autoreactivity of SCH94.03 with endogenous mouse tissue using immunoperoxide and multiple-color immunofluorescence staining techniques on frozen tissue sections. Within the nervous system, SCH94.03 labeled fibrous astrocytes, ependymal cells, ganglion satellite cells, and a sub-population of microglia, oligodendrocytes, and peripheral nervous system neurons. Outside the nervous system, SCH94.03 labeled gastrointestinal tract smooth muscle and luminal epithelium, erythrocytes, and interdigitating dendritic cells in peripheral lymphoid organs. These data indicate that SCH94.03 is a multi-organ reactive autoantibody and support the hypothesis that autoantibodies can have a beneficial rather than a pathogenic function in central nervous system demyelinating diseases.

摘要

与自身免疫和免疫病理学之间的经典关联不同,当代对自身免疫的观点认为自身反应性是一种正常现象。我们之前已经证明,单克隆抗体SCH94.03是一种对多种纯化蛋白和半抗原具有多反应性的天然自身抗体,当将其被动转移到慢性感染泰勒氏鼠脑脊髓炎病毒(一种既定的多发性硬化症实验模型)的SJL/J小鼠体内时,可促进中枢神经系统的髓鞘再生。在本研究中,我们使用免疫过氧化物和多色免疫荧光染色技术,在冷冻组织切片上对SCH94.03与内源性小鼠组织的自身反应性进行了表征。在神经系统内,SCH94.03标记了纤维状星形胶质细胞、室管膜细胞、神经节卫星细胞以及小胶质细胞、少突胶质细胞和外周神经系统神经元的一个亚群。在神经系统外,SCH94.03标记了胃肠道平滑肌和腔上皮、红细胞以及外周淋巴器官中的交错突细胞。这些数据表明SCH94.03是一种多器官反应性自身抗体,并支持自身抗体在中枢神经系统脱髓鞘疾病中可能具有有益而非致病功能的假说。

相似文献

1
Multi-organ reactivity of a monoclonal natural autoantibody that promotes remyelination in a mouse model of multiple sclerosis.一种单克隆天然自身抗体在多发性硬化症小鼠模型中促进髓鞘再生的多器官反应性。
J Histochem Cytochem. 1996 Sep;44(9):1005-11. doi: 10.1177/44.9.8773566.
2
A monoclonal natural autoantibody that promotes remyelination suppresses central nervous system inflammation and increases virus expression after Theiler's virus-induced demyelination.一种促进髓鞘再生的单克隆天然自身抗体可抑制中枢神经系统炎症,并在泰勒氏病毒诱导脱髓鞘后增加病毒表达。
Int Immunol. 1996 Jan;8(1):131-41. doi: 10.1093/intimm/8.1.131.
3
A monoclonal autoantibody that promotes central nervous system remyelination in a model of multiple sclerosis is a natural autoantibody encoded by germline immunoglobulin genes.一种在多发性硬化症模型中促进中枢神经系统重新髓鞘化的单克隆自身抗体是一种由种系免疫球蛋白基因编码的天然自身抗体。
J Immunol. 1995 Mar 1;154(5):2460-9.
4
Monoclonal autoantibodies promote central nervous system repair in an animal model of multiple sclerosis.单克隆自身抗体在多发性硬化症动物模型中促进中枢神经系统修复。
J Neurosci. 1994 Oct;14(10):6230-8. doi: 10.1523/JNEUROSCI.14-10-06230.1994.
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Monoclonal autoantibody SCH94.03, which promotes central nervous system remyelination, recognizes an antigen on the surface of oligodendrocytes.促进中枢神经系统重新髓鞘化的单克隆自身抗体SCH94.03可识别少突胶质细胞表面的一种抗原。
J Neurosci Res. 1996 Feb 1;43(3):273-281. doi: 10.1002/(SICI)1097-4547(19960201)43:3<273::AID-JNR2>3.0.CO;2-G.
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A monoclonal autoantibody which promotes central nervous system remyelination is highly polyreactive to multiple known and novel antigens.一种促进中枢神经系统重新髓鞘化的单克隆自身抗体对多种已知和新抗原具有高度多反应性。
J Neuroimmunol. 1996 Mar;65(1):11-9. doi: 10.1016/0165-5728(95)00175-1.
7
Monoclonal remyelination-promoting natural autoantibody SCH 94.03: pharmacokinetics and in vivo targets within demyelinated spinal cord in a mouse model of multiple sclerosis.单克隆促髓鞘再生天然自身抗体SCH 94.03:在多发性硬化症小鼠模型中脱髓鞘脊髓内的药代动力学及体内靶点
J Neurol Sci. 1997 Sep 10;150(2):103-13. doi: 10.1016/s0022-510x(97)00080-4.
8
Targeting of IgMkappa antibodies to oligodendrocytes promotes CNS remyelination.将IgMκ抗体靶向少突胶质细胞可促进中枢神经系统的髓鞘再生。
J Neurosci. 1998 Oct 1;18(19):7700-8. doi: 10.1523/JNEUROSCI.18-19-07700.1998.
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Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination.溶血卵磷脂诱导的脱髓鞘中中枢神经系统髓鞘再生速率的加速。
J Neurosci. 1998 Apr 1;18(7):2498-505. doi: 10.1523/JNEUROSCI.18-07-02498.1998.
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Successful treatment of established relapsing experimental autoimmune encephalomyelitis in mice with a monoclonal natural autoantibody.用单克隆天然自身抗体成功治疗已建立的小鼠复发性实验性自身免疫性脑脊髓炎。
J Neuroimmunol. 1997 May;75(1-2):204-9. doi: 10.1016/s0165-5728(97)00027-1.

引用本文的文献

1
Do Antibodies Stimulate Myelin Repair in Multiple Sclerosis?抗体是否能刺激多发性硬化症中的髓鞘修复?
Neuroscientist. 1999;5(1):19-28. doi: 10.1177/107385849900500104.
2
Method of identifying natural antibodies for remyelination.鉴定髓鞘再生天然抗体的方法。
J Clin Immunol. 2010 May;30 Suppl 1(0 1):S50-5. doi: 10.1007/s10875-010-9406-5.
3
Cellular mechanisms of central nervous system repair by natural autoreactive monoclonal antibodies.天然自身反应性单克隆抗体修复中枢神经系统的细胞机制
Arch Neurol. 2009 Dec;66(12):1456-9. doi: 10.1001/archneurol.2009.262.
4
Invited article: human natural autoantibodies in the treatment of neurologic disease.特邀文章:人类天然自身抗体在神经系统疾病治疗中的应用
Neurology. 2009 Apr 7;72(14):1269-76. doi: 10.1212/01.wnl.0000345662.05861.e4.
5
Targeting of IgMkappa antibodies to oligodendrocytes promotes CNS remyelination.将IgMκ抗体靶向少突胶质细胞可促进中枢神经系统的髓鞘再生。
J Neurosci. 1998 Oct 1;18(19):7700-8. doi: 10.1523/JNEUROSCI.18-19-07700.1998.