Mader Simone, Brimberg Lior, Diamond Betty
The Feinstein Institute for Medical Research, The Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, Northwell Health System, Manhasset, NY, United States.
Front Immunol. 2017 Sep 11;8:1101. doi: 10.3389/fimmu.2017.01101. eCollection 2017.
Antibodies to different brain proteins have been recently found to be associated with an increasing number of different autoimmune diseases. They need to penetrate the blood-brain barrier (BBB) in order to bind antigens within the central nervous system (CNS). They can target either neuronal or non-neuronal antigen and result in damage either by themselves or in synergy with other inflammatory mediators. Antibodies can lead to acute brain pathology, which may be reversible; alternatively, they may trigger irreversible damage that persists even though the antibodies are no longer present. In this review, we will describe two different autoimmune conditions and the role of their antibodies in causing brain pathology. In systemic lupus erythematosus (SLE), patients can have double stranded DNA antibodies that cross react with the neuronal -methyl-d-aspartate receptor (NMDAR), which have been recently linked to neurocognitive dysfunction. In neuromyelitis optica (NMO), antibodies to astrocytic aquaporin-4 (AQP4) are diagnostic of disease. There is emerging evidence that pathogenic T cells also play an important role for the disease pathogenesis in NMO since they infiltrate in the CNS. In order to enable appropriate and less invasive treatment for antibody-mediated diseases, we need to understand the mechanisms of antibody-mediated pathology, the acute and chronic effects of antibody exposure, if the antibodies are produced intrathecally or systemically, their target antigen, and what triggers their production. Emerging data also show that exposure to some brain-reactive antibodies, such as those found in SLE, can cause neurodevelopmental impairment since they can penetrate the embryonic BBB. If the antibody exposure occurs at a critical time of development, this can result in irreversible damage of the offspring that persists throughout adulthood.
最近发现，针对不同脑蛋白的抗体与越来越多的不同自身免疫性疾病相关。它们需要穿透血脑屏障（BBB）才能结合中枢神经系统（CNS）内的抗原。它们可以靶向神经元或非神经元抗原，并单独或与其他炎症介质协同作用导致损伤。抗体可导致急性脑病变，这可能是可逆的；或者，它们可能引发不可逆的损伤，即使抗体不再存在，这种损伤仍会持续。在这篇综述中，我们将描述两种不同的自身免疫性疾病及其抗体在导致脑病变中的作用。在系统性红斑狼疮（SLE）中，患者可产生与神经元N-甲基-D-天冬氨酸受体（NMDAR）发生交叉反应的双链DNA抗体，最近已发现其与神经认知功能障碍有关。在视神经脊髓炎（NMO）中，针对星形胶质细胞水通道蛋白4（AQP4）的抗体是该病的诊断依据。有新证据表明，致病性T细胞在NMO的疾病发病机制中也起重要作用，因为它们会浸润中枢神经系统。为了对抗体介导的疾病进行适当且侵入性较小的治疗，我们需要了解抗体介导病变的机制、抗体暴露的急性和慢性影响、抗体是鞘内还是全身产生的、其靶抗原以及触发其产生的因素。新数据还表明，接触某些脑反应性抗体，如在SLE中发现的那些抗体，可导致神经发育障碍，因为它们可以穿透胚胎血脑屏障。如果在发育的关键时期发生抗体暴露，这可能导致后代不可逆转的损伤，并持续至成年期。
