Neurofascin antibodies in autoimmune, genetic, and idiopathic neuropathies.
Neurofascin antibodies in autoimmune, genetic, and idiopathic neuropathies.
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DOI：
10.1212/wnl.0000000000004773
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发表时间：
2018-01-02
期刊：
影响因子：
9.9
通讯作者：
Lancaster E
中科院分区：
文献类型：
--
作者：
Burnor E;Yang L;Zhou H;Patterson KR;Quinn C;Reilly MM;Rossor AM;Scherer SS;Lancaster E
目的：检测周围神经病患者中神经束蛋白抗体的频率、持久性、异构体特异性和临床相关性。我们研究了格林-巴利综合征(GBS)或慢性炎症性脱髓鞘多神经病(CIDP)(n=59)、遗传性神经病(n=111)和特发性神经病(n=43)患者的免疫球蛋白(Ig)G和IgM对3种神经纤维素亚单位(NF140、NF155和NF186)的反应。神经束素抗体在GBS/CIDP患者中的发生率(14%，8/59)高于遗传性神经病对照组(3%，3/111，P=0.01)。7%的特发性神经病患者(43人中有3人)也有神经束素抗体。NF155 IgG4抗体与对IV免疫球蛋白无效但对利妥昔单抗有效的CIDP有关，其中一些患者的急性发作类似于GBS。NF186对任何一种异构体的免疫球蛋白和免疫球蛋白的特异性较差。在一名抗体可识别所有三种神经束蛋白亚型的患者中，发现一种接近锁定状态的严重的CIDP。在自身免疫性神经病样本中，神经束素抗体的出现频率是遗传性神经病对照组的4倍。对NF155的持续IgG4应答与对常规治疗的严重CIDP耐药有关，但对利妥昔单抗有反应。针对神经胶质和轴突异构体共有的共同结构域的IgG4抗体可能预示着一种特别严重但可治疗的神经病。神经束素抗体在特发性神经病患者亚组中的预后意义和GBS中的一过性IgM反应需要进一步研究。
To measure the frequency, persistence, isoform specificity, and clinical correlates of neurofascin antibodies in patients with peripheral neuropathies. We studied cohorts of patients with Guillain-Barre syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) (n = 59), genetic neuropathy (n = 111), and idiopathic neuropathy (n = 43) for immunoglobulin (Ig) G and IgM responses to 3 neurofascin (NF) isoforms (NF140, NF155, and NF186) using cell-based assays. Neurofascin antibodies were more common in patients with GBS/CIDP (14%, 8 of 59) compared to genetic neuropathy controls (3%, 3 of 111, p = 0.01). Seven percent (3 of 43) of patients with idiopathic neuropathy also had neurofascin antibodies. NF155 IgG4 antibodies were associated with CIDP refractory to IV immunoglobulin but responsive to rituximab, and some of these patients had an acute onset resembling GBS. NF186 IgG and IgM to either isoform were less specific. A severe form of CIDP, approaching a locked-in state, was seen in a patient with antibodies recognizing all 3 neurofascin isoforms. Neurofascin antibodies were 4 times more frequent in autoimmune neuropathy samples compared to genetic neuropathy controls. Persistent IgG4 responses to NF155 correlated with severe CIDP resistant to usual treatments but responsive to rituximab. IgG4 antibodies against the common domains shared by glial and axonal isoforms may portend a particularly severe but treatable neuropathy. The prognostic implications of neurofascin antibodies in a subset of idiopathic neuropathy patients and transient IgM responses in GBS require further investigation.