Correale Jorge, de los Milagros Bassani Molinas María
Departmento de Neurología, Instituto de Investigaciones Neurológicas, Dr Raúl Carrea, Buenos Aires, Argentina.
J Neurol. 2002 Apr;249(4):375-89. doi: 10.1007/s004150200026.
Multiple Sclerosis (MS) is an inflammatory disease of the Central Nervous System with multifocal areas of demyelination. Although its etiology and pathogenesis remain controversial, several lines of evidence indicate that MS is mediated by a misdirected immune response against one or several myelin proteins. The involvement of diverse leukocyte subsets and their products in MS is still the subject of considerable debate. The emphasis on T cells has derived mainly from the detection of activated T cells in MS plaques and analogies with animal models of MS. Because of these observations cell-mediated immunity has dominated the research field of MS to this day. However, in recent years the role of B cells, plasma cells and immunoglobulins in MS have been re-examined, and current findings indicate that humoral immunity also plays a major role in disease pathogenesis. B cells and their products could exert several potential effects during the course of MS. Firstly, autoantibodies against specific myelin antigens could mediate damage to myelin membranes. Secondly, some studies suggest that natural autoantibodies could enhance remyelination. Thirdly, antibodies directed against myelin components can participate in anti-idiotypic networks, which may regulate the course of MS. Increased intrathecal immunoglobulin synthesis reflected by raised IgG indices and an oligoclonal pattern is the most common abnormality detected in MS patients. The introduction of more sensitive procedures for protein detection has allowed demonstrating oligoclonal bands (OCBs) in up to 95 % of patients with clinically definite MS. Although the presence of OCBs in CSF of MS patients is now well established as a sensitive laboratory test to support the clinical diagnosis, OCBs may be present in other disorders, including those not directly related to infection or abnormal immune response. Nevertheless, the pathogenesis of OCBs in MS is still obscure, and despite extensive research their antigenic target(s) have yet to be established. Therefore, a critical task is to identify the specificity of such target(s), thus providing significant clues about MS etiology. For this purpose, novel molecular immunologic strategies have been recently developed to offer alternative approaches to identify putative antigens recognized by antibodies present in MS patients. The elucidation of the mechanisms and target(s) responsible for the onset of MS has obvious implications for the further development of specific therapies.
多发性硬化症（MS）是一种中枢神经系统的炎症性疾病，具有多灶性脱髓鞘区域。尽管其病因和发病机制仍存在争议，但多项证据表明，MS是由针对一种或几种髓鞘蛋白的错误定向免疫反应介导的。多种白细胞亚群及其产物在MS中的作用仍是相当多争论的主题。对T细胞的重视主要源于在MS斑块中检测到活化的T细胞以及与MS动物模型的类比。由于这些观察结果，细胞介导的免疫至今在MS研究领域占据主导地位。然而，近年来，B细胞、浆细胞和免疫球蛋白在MS中的作用已被重新审视，目前的研究结果表明体液免疫在疾病发病机制中也起主要作用。B细胞及其产物在MS病程中可能发挥多种潜在作用。首先，针对特定髓鞘抗原的自身抗体可介导对髓鞘膜的损伤。其次，一些研究表明天然自身抗体可促进髓鞘再生。第三，针对髓鞘成分的抗体可参与抗独特型网络，这可能调节MS的病程。IgG指数升高和寡克隆模式反映的鞘内免疫球蛋白合成增加是在MS患者中检测到的最常见异常。蛋白质检测更敏感方法的引入使得在高达95%的临床确诊MS患者中能够检测到寡克隆带（OCB）。尽管MS患者脑脊液中OCB的存在现在已被公认为支持临床诊断的敏感实验室检查，但OCB可能存在于其他疾病中，包括那些与感染或异常免疫反应无直接关系的疾病。然而，MS中OCB的发病机制仍然不清楚，尽管进行了广泛研究，其抗原靶点尚未确定。因此，一项关键任务是确定此类靶点的特异性，从而为MS病因提供重要线索。为此，最近开发了新的分子免疫学策略，以提供替代方法来识别MS患者体内抗体识别的假定抗原。阐明导致MS发病的机制和靶点对特定疗法的进一步发展具有明显意义。
