A model for lupus brain disease.
A model for lupus brain disease.
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DOI：
10.1111/j.1600-065x.2012.01137.x
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发表时间：
2012-07
影响因子：
8.7
通讯作者：
Volpe BT
中科院分区：
文献类型：
--
作者：
Diamond B;Volpe BT
系统性红斑狼疮是一种自身免疫性疾病，其特征是抗体结合体内多个器官的目标自身抗原。在外周器官中，免疫复合物参与补体级联反应，招募血源性炎症细胞并引发组织炎症。免疫复合物介导的Fc受体对浸润性血源性细胞和组织驻留细胞的激活放大了炎症级联反应，导致组织功能受损，最终导致组织破坏。这种病理生理学似乎可以解释除中枢神经系统外的全身组织损伤。这篇综述阐述了我们为自身抗体介导的脑损伤开发的一种范式。这一模式表明，抗体介导的脑部疾病并不依赖于免疫复合物的形成，而是依赖于抗体介导的神经元激活和存活的改变。此外，抗体只有在血脑屏障完整性受损时才能进入脑组织，从而导致脑部疾病和其他器官的组织损伤不会同时发生。我们讨论了该模型对狼疮和其他可能导致脑部疾病的抗体的影响。
Systemic lupus erythematosus is an autoimmune disease characterized by antibodies that bind target autoantigens in multiple organs in the body. In peripheral organs, immune complexes engage the complement cascade, recruiting blood-borne inflammatory cells and initiating tissue inflammation. Immune complex-mediated activation of Fc receptors on infiltrating blood-borne cells and tissue resident cells amplifies an inflammatory cascade with resulting damage to tissue function, ultimately leading to tissue destruction. This pathophysiology appears to explain tissue injury throughout the body, except in the central nervous system. This review addresses a paradigm we have developed for autoantibody-mediated brain damage. This paradigm suggests that antibody-mediated brain disease does not depend on immune complex formation but rather on antibody-mediated alterations in neuronal activation and survival. Moreover, antibodies only access brain tissue when blood-brain barrier integrity is impaired, leading to a lack of concurrence of brain disease and tissue injury in other organs. We discuss the implications of this model for lupus and for identifying other antibodies that may contribute to brain disease.