Most cases of neuromyelitis optica spectrum disorders (NMOSD) harbor pathogenic autoantibodies against the water channel aquaporin 4 (AQP4). Binding of these antibodies to AQP4 on astrocytes initiates damage to these cells, which culminates in the formation of large tissue destructive lesions in the central nervous system (CNS). Consequently, untreated patients may become permanently blind or paralyzed. Studies on the induction and breakage of tolerance to AQP4 could be of great benefit for NMOSD patients. So far, however, all attempts to create suitable animal models by active sensitization have failed. We addressed this challenge and identified peptides, which mimic the conformational AQP4 epitopes recognized by pathogenic antibodies of NMOSD patients. Here we show that these mimotopes can induce the production of AQP4-reactive antibodies in Lewis rats. Hence, our results provide a conceptual framework for the formation of such antibodies in NMOSD patients, and aid to improve immunization strategies for the creation of animal models suitable for tolerance studies in this devastating disease.

中文翻译：

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在用水通道蛋白4模拟表位免疫的Lewis大鼠中诱导水通道蛋白4反应性抗体。

视神经脊髓炎光谱疾病（NMOSD）的大多数病例都带有针对水通道水通道蛋白4（AQP4）的致病性自身抗体。这些抗体与星形胶质细胞上的AQP4结合会引发对这些细胞的损害，最终导致中枢神经系统（CNS）形成大型组织破坏性病变。因此，未经治疗的患者可能会永久失明或瘫痪。对AQP4耐受性的诱导和破坏的研究可能对NMOSD患者有很大的帮助。然而，到目前为止，所有通过主动敏化创建合适的动物模型的尝试都失败了。我们解决了这一挑战并鉴定了肽，该肽模拟了NMOSD患者的病原性抗体识别的构象AQP4表位。在这里，我们显示这些模拟表位可以诱导Lewis大鼠中AQP4反应性抗体的产生。因此，我们的结果为在NMOSD患者中形成此类抗体提供了概念框架，并有助于改善免疫策略，以创建适合于在这种毁灭性疾病中进行耐受性研究的动物模型。