From the Department of Neurology (H.S., A.M.B., L.A., B.F., A.P., C.S., K.D.), University Hospital Würzburg; Institute of Clinical Neuroimmunology (A.V., E.M.), Biomedical Center, University Hospitals, Ludwig-Maximilians-Universität München, Planegg-Martinsried; Universitätsklinikum Schleswig-Holstein Campus Kiel (A.H., F.L.), Neuroimmunology Section, Institute of Clinical Chemistry, Kiel/Lübeck; Department of Neurology (F.G.), University Hospital Halle; Department of Neurology (C.D., F.B.), University Hospital Mainz, Mainz; University Hospital Aachen (J.W.), Institute of Neuropathology, Aachen; Department of Neurology (T.H., P.K.), University Hospital Magdeburg; Institute for Pharmacology and Toxicology (C.S.), Otto-von-Guericke University; German Center for Neurodegenerative Diseases (P.K.), Magdeburg; Institute for Clinical Neurobiology (C.V.), University Hospital Würzburg; Department of Neurology (F.L.), Universitätsklinikum Schleswig-Holstein, Kiel, Germany; and Research Center for Translational Medicine (A.V), Koç University, Istanbul, Turkey.
Neurol Neuroimmunol Neuroinflamm. 2019 Aug 16;6(5). doi: 10.1212/NXI.0000000000000603. Print 2019 Sep.
To identify and characterize patients with autoantibodies against different neurofascin (NF) isoforms.
Screening of a large cohort of patient sera for anti-NF autoantibodies by ELISA and further characterization by cell-based assays, epitope mapping, and complement binding assays.
Two different clinical phenotypes became apparent in this study: The well-known clinical picture of subacute-onset severe sensorimotor neuropathy with tremor that is known to be associated with IgG4 autoantibodies against the paranodal isoform NF-155 was found in 2 patients. The second phenotype with a dramatic course of disease with tetraplegia and almost locked-in syndrome was associated with IgG3 autoantibodies against nodal and paranodal isoforms of NF in 3 patients. The epitope against which these autoantibodies were directed in this second phenotype was the common Ig domain found in all 3 NF isoforms. In contrast, anti-NF-155 IgG4 were directed against the NF-155-specific Fn3Fn4 domain. The description of a second phenotype of anti-NF-associated neuropathy is in line with some case reports of similar patients that were published in the last year.
Our results indicate that anti-pan-NF-associated neuropathy differs from anti-NF-155-associated neuropathy, and epitope and subclass play a major role in the pathogenesis and severity of anti-NF-associated neuropathy and should be determined to correctly classify patients, also in respect to possible differences in therapeutic response.
鉴定并描述针对不同神经束蛋白（NF）同种型的自身抗体患者。
通过 ELISA 对大量患者血清进行抗 NF 自身抗体筛查，并通过基于细胞的检测、表位作图和补体结合检测进行进一步鉴定。
本研究中出现了两种不同的临床表型：2 例患者表现为众所周知的亚急性发作严重感觉运动神经病伴震颤，与针对神经束蛋白 155 （NF-155） 连接蛋白同种型的 IgG4 自身抗体相关；3 例患者出现急剧进展的疾病，表现为四肢瘫痪和几乎闭锁综合征，与针对 NF 节段和连接蛋白同种型的 IgG3 自身抗体相关。针对这第二种表型的自身抗体的表位是所有 3 种 NF 同种型中共有的 Ig 结构域。相比之下，抗 NF-155 IgG4 针对的是 NF-155 特异性的 Fn3Fn4 结构域。抗 NF 相关神经病的第二种表型的描述与去年发表的类似患者的一些病例报告一致。
我们的研究结果表明，与 NF-155 相关的神经病不同，针对泛 NF 的神经病，表位和亚类在抗 NF 相关神经病的发病机制和严重程度中起主要作用，应确定这些表位和亚类以正确分类患者，也应考虑到治疗反应的可能差异。
