Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Center for Brain Research, Medical University of Vienna, Vienna, Austria.
Acta Neuropathol Commun. 2015 Dec 4;3:80. doi: 10.1186/s40478-015-0260-9.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Immunological studies suggest that it is a T-cell mediated autoimmune disease, although an MS-specific target antigen for autoimmunity has so far not been identified. Models of experimental autoimmune encephalomyelitis in part reproduce features of MS, but none of the models so far covers the entire spectrum of pathology and immunology. Autoimmune disease of the nervous system has occasionally been observed in humans after active sensitization with brain tissue or brain cells, giving rise to acute demyelinating polyradiculoneuritis, acute disseminated encephalomyelitis and in rare cases reflecting an inflammatory demyelinating condition similar to acute multiple sclerosis. In this study we analyzed in detail the immunopathology in archival autopsy tissue of a patient who died with an MS like disease after repeated exposure to subcutaneous injections of lyophilized brain cells.
The pathology of this patient fulfilled all pathological diagnostic criteria of MS. Demyelination and tissue injury was associated with antibody (IgM) deposition at active lesion sites and complement activation. Major differences to classical EAE models were seen in the composition of inflammatory infiltrates, being dominated by B-cells, infiltration of IgM positive plasma cells, profound infiltration of the tissue by CD8(+) T-lymphocytes and a nearly complete absence of CD4(+) T-cells.
Our study shows that auto-sensitization of humans with brain tissue can induce a disease, which closely reflects the pathology of MS, but that the mechanisms leading to demyelination and tissue injury differ from those, generally implicated in the pathophysiology of MS through studies in experimental autoimmune encephalomyelitis.
多发性硬化症（MS）是一种中枢神经系统的慢性炎症性脱髓鞘疾病。免疫学研究表明，它是一种 T 细胞介导的自身免疫性疾病，尽管迄今为止尚未确定自身免疫的 MS 特异性靶抗原。实验性自身免疫性脑脊髓炎的模型在一定程度上再现了 MS 的特征，但到目前为止，没有一种模型涵盖了病理学和免疫学的全部范围。在主动用脑组织或脑细胞致敏后，人类偶尔会出现神经系统自身免疫性疾病，导致急性脱髓鞘性多神经根神经炎、急性播散性脑脊髓炎，在极少数情况下，反映出类似于急性多发性硬化症的炎症性脱髓鞘疾病。在这项研究中，我们详细分析了一名患者的存档尸检组织的免疫病理学，该患者在反复皮下注射冻干脑细胞后死于类似 MS 的疾病。
该患者的病理学符合 MS 的所有病理诊断标准。脱髓鞘和组织损伤与活性病变部位的抗体（IgM）沉积和补体激活有关。与经典 EAE 模型的主要区别在于炎症浸润物的组成，以 B 细胞为主，IgM 阳性浆细胞浸润，CD8(+)T 淋巴细胞大量浸润，CD4(+)T 细胞几乎完全缺失。
我们的研究表明，用脑组织对人体进行自身致敏可以诱导一种疾病，该疾病与 MS 的病理学密切相关，但导致脱髓鞘和组织损伤的机制与通过实验性自身免疫性脑脊髓炎研究中一般涉及 MS 病理生理学的机制不同。
