Chronic Inflammatory Demyelinating Polyneuropathy With Concurrent Membranous Nephropathy: An Anti-paranode and Podocyte Protein Antibody Study and Literature Survey
Chronic Inflammatory Demyelinating Polyneuropathy With Concurrent Membranous Nephropathy: An Anti-paranode and Podocyte Protein Antibody Study and Literature Survey
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DOI：
10.3389/fneur.2018.00997
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发表时间：
2018-11-27
影响因子：
3.4
通讯作者：
Kira, Jun-ichi
中科院分区：
文献类型：
--
作者：
Hashimoto, Yu;Ogata, Hidenori;Kira, Jun-ichi
背景：一些病例报告描述了慢性炎症性脱髓鞘性多发性神经病（CIDP）和膜性肾病（MN）同时发生的情况。膜性肾病中存在针对足细胞抗原磷脂酶A2受体（PLA2R）和含Ⅰ型血小板反应蛋白结构域7A（THSD7A）的自身抗体，这提示存在一种自身免疫机制。一些CIDP患者也携带针对结旁蛋白的自身抗体，如神经束蛋白155（NF155）和接触蛋白 - 1（CNTN1）。我们通过检测一名患有MN的CIDP患者中针对结旁和足细胞抗原的自身抗体，并对伴有MN的CIDP的临床特征进行文献综述，来研究CIDP和MN之间的关系。
方法：使用稳定表达人CNTN1或NF155的HEK293细胞系，通过流式细胞术检测抗CNTN1和NF155抗体。通过对小鼠坐骨神经纤维进行免疫染色来验证抗体的结合能力。通过酶联免疫吸附测定法检测抗PLA2R抗体，通过间接免疫荧光测定法检测抗THSD7A抗体。比较了14例伴有MN的CIDP病例（包括2例抗CNTN1抗体阳性病例）和20例抗CNTN1抗体阳性的CIDP病例的临床特征。
结果：一名70多岁的患者主诉四肢进行性无力以及浅感觉和深感觉障碍，病程超过6个月。神经传导研究显示明显的脱髓鞘模式。患者表现为肾病综合征。肾活检显示基底膜增厚，伴有局部上皮下突起以及IgG4在肾小球沉积，符合MN。自身抗体检测显示存在IgG4和IgG1抗CNTN1抗体，但不存在抗NF155、抗PLA2R和抗THSD7A抗体。患者的血清可使坐骨神经纤维的结旁染色。伴有MN且抗CNTN1抗体阳性的CIDP通常表现为男性居多、发病年龄相对较高、35 - 50%的病例为急性至亚急性起病、以远端为主的感觉运动神经病、本体感觉障碍导致感觉性共济失调以及脑脊液蛋白水平非常高。然而，13例伴有MN的CIDP患者中有11例对单一或联合免疫疗法反应良好，而抗CNTN1抗体阳性的CIDP对皮质类固醇和静脉注射免疫球蛋白治疗常常耐药。
结论：伴有MN的CIDP和抗CNTN1抗体阳性的CIDP有相当多的重叠，但并不完全相同。伴有MN的CIDP可能具有异质性，一些病例携带抗CNTN1抗体。
Background: Several case reports have described the concurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN). The presence of autoantibodies against podocyte antigens phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) in MN suggests an autoimmune mechanism. Some CIDP patients also harbor autoantibodies against paranodal proteins such as neurofascin 155 (NF155) and contactin-1 (CNTN1). We investigated the relationship between CIDP and MN by assaying autoantibodies against paranodal and podocyte antigens in a CIDP patient with MN, and by a literature survey on the clinical features of CIDP with MN.Methods: Anti-CNTN1 and NF155 antibodies were measured by flow cytometry using HEK293 cell lines stably expressing human CNTN1 or NF155. Binding capacity of antibodies was validated by immunostaining mouse teased sciatic nerve fibers. Anti-PLA2R antibodies were measured by enzyme-linked sorbent assay and anti-THSD7A antibodies by indirect immunofluorescence assay. Clinical features between 14 CIDP with MN cases including two with anti-CNTN1 antibodies and 20 anti-CNTN1 antibody-positive CIDP cases were compared.Results: A patient whose ages was in the late 70 s complained of progressive weakness and superficial and deep sensory impairment in four extremities over 6 months. Nerve conduction studies showed prominent demyelination patterns. The patient presented with nephrotic syndrome. Renal biopsy disclosed basement membrane thickening with local subepithelial projections and glomerular deposits of IgG4, compatible with MN. Autoantibody assays revealed the presence of IgG4 and IgG1 anti-CNTN1 antibodies, but an absence of anti-NF155, anti-PLA2R, and anti-THSD7A antibodies. The patient's serum stained paranodes of teased sciatic nerves. CIDP with MN and anti-CNTN1 antibody-positive CIDP commonly showed male preponderance, relatively higher age of onset, acute to subacute onset in 35-50% of cases, distal dominant sensorimotor neuropathy, proprioceptive impairment leading to sensory ataxia, and very high cerebrospinal fluid protein levels. However, 11 of 13 CIDP patients with MN had a favorable response to mono-or combined immunotherapies whereas anti-CNTN1 antibody-positive CIDP was frequently refractory to corticosteroids and intravenous immunoglobulin administration.Conclusion: CIDP with MN and anti-CNTN1 antibody-positive CIDP show considerable overlap but are not identical. CIDP with MN is probably heterogeneous and some cases harbor anti-CNTN1 antibodies.