Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Exp Neurol. 2013 Sep;247:259-66. doi: 10.1016/j.expneurol.2013.05.005. Epub 2013 May 18.
Axonal injury is considered the major cause of chronic disability in multiple sclerosis (MS) patients, however the mechanisms behind remain still unclear. Recently, it was demonstrated that autoantibodies against Neurofascin, a cell adhesion molecule within the adult nervous system, can contribute to the development of axonal pathology in some patients. We compared the ability of the two different isoforms of Neurofascin, Nfasc155 and Nfasc186, to induce a pathogenic antibody response in the Dark Agouti (DA) rat. Animals were immunized with recombinant proteins prior to induction of experimental autoimmune encephalomyelitis (EAE) by adoptive transfer of activated MOG-specific T cells. Only Nfasc186 induced an axopathic autoantibody response in vivo, despite extensive cross reactivity between the two isoforms as shown by ELISA and flow cytometry. In this case, using transfected cell lines failed to differentiate between pathogenic and non-pathogenic responses. These findings have important implications with respect to the usage of cell based assays as an approach to detect pathologically relevant autoantibodies in clinical samples.
轴突损伤被认为是多发性硬化症（MS）患者慢性残疾的主要原因，但背后的机制仍不清楚。最近，研究表明，针对神经束蛋白（一种成年神经系统中的细胞黏附分子）的自身抗体可能导致某些患者的轴突病理发生。我们比较了神经束蛋白的两种不同亚型，Nfasc155 和 Nfasc186，在诱导 Dark Agouti（DA）大鼠产生致病性抗体反应方面的能力。在通过过继转移活化的 MOG 特异性 T 细胞诱导实验性自身免疫性脑脊髓炎（EAE）之前，用重组蛋白对动物进行免疫。只有 Nfasc186 在体内诱导了一种轴突病自身抗体反应，尽管两种亚型之间存在广泛的交叉反应，如 ELISA 和流式细胞术所示。在这种情况下，使用转染细胞系未能区分致病性和非致病性反应。这些发现对于将基于细胞的检测作为在临床样本中检测病理性相关自身抗体的方法的使用具有重要意义。
