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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Anti-DNA antibodies are a major component of the intrathecal B cell response in multiple sclerosis
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Anti-DNA antibodies are a major component of the intrathecal B cell response in multiple sclerosis

机译：抗DNA抗体是多发性硬化症鞘内B细胞反应的主要成分

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摘要

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of unknown cause that afflicts the central nervous system. MS is typified by a highly clonally restricted antigen-driven anti- body response that is confined largely to the central nervous system. The major antigenic targets of this response and the role of antibody in disease pathogenesis remain unclear. To help resolve these issues, we cloned the IgG repertoire directly from active plaque and periplaque regions in MS brain and from B cells recovered from the cerebrospinal fluid of a patient with MS with subacute disease. We found that high-affinity anti-DNA antibodies are a major component of the intrathecal IgG response in the patients with MS that we studied. Furthermore. we show DNA- specific monoclonal antibodies rescued from two subjects with MS as well as a DNA-specific antibody rescued from an individual suffering from systemic lupus erythematosus bound efficiently to the surface of neuronal cells and oligodendrocytes. For two of these antibodies, cell-surface recognition was DNA dependent. Our findings indicate that anti-DNA antibodies may promote important neuropathologic mechanisms in chronic inflammatory disorders, such as MS and systemic lupus erythematosus.
机译：多发性硬化症（MS）是一种原因不明的慢性炎症性脱髓鞘疾病，困扰着中枢神经系统。 MS的典型特征是高度克隆限制的抗原驱动的抗体反应，该反应主要局限于中枢神经系统。尚不清楚此反应的主要抗原靶标和抗体在疾病发病机理中的作用。为了帮助解决这些问题，我们直接从MS脑中的活动斑块和周围斑块区域以及从患有亚急性疾病的MS患者的脑脊液中回收的B细胞克隆了IgG库。我们发现，在我们研究的MS患者中，高亲和力抗DNA抗体是鞘内IgG反应的主要成分。此外。我们显示了从两名患有MS的受试者中拯救出的DNA特异性单克隆抗体，以及从有效地结合到神经元细胞和少突胶质细胞表面的全身性红斑狼疮患者获得的DNA特异性抗体。对于这些抗体中的两种，细胞表面识别是DNA依赖性的。我们的发现表明，抗DNA抗体可能会促进慢性炎症性疾病（例如MS和系统性红斑狼疮）的重要神经病理机制。

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