Autoimmunity due to molecular mimicry as a cause of neurological disease
Autoimmunity due to molecular mimicry as a cause of neurological disease
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DOI：
10.1038/nm0502-509
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发表时间：
2002-05-01
期刊：
影响因子：
82.9
通讯作者：
Stuart, JM
中科院分区：
文献类型：
--
作者：
Levin, MC;Lee, SM;Stuart, JM
一种假设是，夫妻感染自身免疫性疾病是分子模仿。分子模仿的特征是对环境因素的免疫反应，该反应与宿主抗原交叉反应，导致疾病(1，2)。这一假说与糖尿病、狼疮和多发性硬化症(MS)的发病机制有关(1-4)。在这些疾病中，将病原体与致病免疫反应联系起来的直接证据有限。我们的研究在病毒感染、自身免疫和人类神经系统疾病之间建立了明确的联系。作为分子模拟的模型，我们研究了人类T淋巴细胞病毒1型(HTLV-1)相关性脊髓病/热带痉挛麻痹(HAM/TSP)患者，这种疾病与MS无法区分(参考文献)。5-7)。HAM/TSP患者产生针对神经元的抗体(8)。我们假设这些抗体将识别中枢神经系统(CNS)自身抗原。从HAM/TSP患者中分离的免疫球蛋白G确定异质性核糖核蛋白A1(hnRNP-A1)为自身抗原。HnRNP-A1抗体与HTLV-1-TAX交叉反应，其免疫反应与HAM/TSP相关(参考文献.5、9)。免疫球蛋白G特异性地染色人类Betz细胞，其轴突优先受损(7)。脑部注射自身抗体抑制了神经元的放电，这表明了其致病性质。这些数据表明了感染剂和hnRNP-A1之间的分子模仿在中枢神经系统自身免疫性疾病中的重要性。
One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease(1,2). This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS)(1-4). There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5-7). HAM/TSP patients develop antibodies to neurons(8). We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5,9). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged(7). Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS.