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[多发性硬化症患者体内自身抗体所识别的髓鞘蛋白表位]

[Epitopes on myelin proteins recognized by autoantibodies present in multiple sclerosis patients].

作者信息

Jaśkiewicz Ewa

机构信息

Zakład Immunochemii,Instytut Immunologii i Terapii Doświadczalnej PAN im.Ludwika Hirszfelda we Wrocławiu.

出版信息

Postepy Hig Med Dosw (Online). 2004;58:472-82.

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). It is thought that autoimmunity plays a major role in the development of the disease. Despite understanding MS as the cell-mediated autoimmune disease, recent studies suggest a role of humoral response in MS pathogenesis. The contribution of antibodies with anti-MOG specificity in the pathology of EAE (experimental allergic encephalomyelitis), an animal model of MS, in rodents and recently in primates has been demonstrated. B lymphocytes, plasma cells, and autoantibodies reacting with myelin proteins are present in the chronic and active plaques of MS patients. These antibodies, which recognize myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), myelin-oligodendrocyte glycoprotein (MOG), oligodendrocyte-specific protein (OSP), 2',3' cyclic nucleotide 3'-phosphodiesterase (CNP), and transaldolase (TAL), have been identified mostly in cerebrospinal fluid and in serum. So far, the antibodies directed against MBP, MOG, and OSP have been characterized in detail. However, the role of autoantibodies in MS pathogenesis is still controversial. A direct role in the demyelination process, by the activation of complement and cytotoxic cells, has been shown only for the anti-MOG antibodies. Identification of the antigens and epitopes targeting the autoimmune response in MS is of great importance, not only for understanding of MS pathology, but also for potential therapeutic use. Recently, antigen therapy trials have been conducted in MS patients. It seems, however, that only the recognition of the individual immunological response in each MS patient, including autoantigens and the subspecificity of autoreactive T and B lymphocytes, can allow for an effective fight against this destructive disease.

摘要

多发性硬化症(MS)是一种中枢神经系统(CNS)的慢性炎症性疾病。人们认为自身免疫在该疾病的发展中起主要作用。尽管MS被认为是细胞介导的自身免疫性疾病,但最近的研究表明体液反应在MS发病机制中也发挥作用。在啮齿动物以及最近在灵长类动物中,已证实具有抗髓鞘少突胶质细胞糖蛋白(MOG)特异性的抗体在实验性自身免疫性脑脊髓炎(EAE,一种MS动物模型)的病理过程中起作用。与髓鞘蛋白反应的B淋巴细胞、浆细胞和自身抗体存在于MS患者的慢性和活动性斑块中。这些识别髓鞘碱性蛋白(MBP)、蛋白脂蛋白(PLP)、髓鞘相关糖蛋白(MAG)、髓鞘少突胶质细胞糖蛋白(MOG)、少突胶质细胞特异性蛋白(OSP)、2',3'环核苷酸3'-磷酸二酯酶(CNP)和转醛醇酶(TAL)的抗体大多在脑脊液和血清中被鉴定出来。到目前为止,针对MBP、MOG和OSP的抗体已得到详细表征。然而,自身抗体在MS发病机制中的作用仍存在争议。仅抗MOG抗体通过补体和细胞毒性细胞的激活在脱髓鞘过程中显示出直接作用。确定MS中针对自身免疫反应的抗原和表位不仅对于理解MS病理学很重要,而且对于潜在的治疗用途也很重要。最近,已在MS患者中进行了抗原治疗试验。然而,似乎只有识别每个MS患者的个体免疫反应,包括自身抗原以及自身反应性T和B淋巴细胞的亚特异性,才能有效地对抗这种破坏性疾病。

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