Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.
Department of Research and Development, Guangzhou Weimi Bio-Tech Co., Ltd, Guangzhou, China.
Front Immunol. 2021 Oct 5;12:759187. doi: 10.3389/fimmu.2021.759187. eCollection 2021.
The concurrence of anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN) has previously been reported in the literature. CIDP with autoantibodies against paranodal proteins are defined as autoimmune nodopathies (AN) in the latest research. In view of the unclear relationship between CIDP and MN, we performed a case study and literature review to investigate the clinical characteristics of anti-CNTN antibody-associated AN with MN.
We detected antibodies against NF155, NF186, CNTN1, CNTN2, CASPR1 and PLA2R in blood samples of a patient with clinically manifested MN and concomitant peripheral neuropathy double immunofluorescence staining and conducted a quantitative measurement of anti-PLA2R IgG antibodies enzyme-linked immunosorbent assay (ELISA). Case reports of anti-CNTN1 antibody-associated AN, anti-CNTN1 antibody-associated AN with MN, and CIDP with MN were retrieved through a literature search for a comparative analysis of clinical characteristics. The cases were grouped according to the chronological order of CIDP and MN onset for the comparison of clinical characteristics.
A 57-year-old man with anti-PLA2R positive MN was admitted to the hospital due to limb numbness, weakness, and proprioceptive sensory disorder. He was diagnosed with anti-CNTN1 antibody-associated AN and recovered well after immunotherapy. Our literature search returned 22 cases of CIDP with MN that occurred before, after, or concurrently with CIDP. Good responses were achieved with early single-agent or combination immunotherapy, but eight out of the 22 patients with CIDP and concomitant MN ultimately developed different motor sequelae. Five patients had anti-CNTN1 antibody-associated AN with MN. Among these patients, males accounted for the majority of cases (male:female=4:1), the mean age at onset was late (60.2 ± 15.7 years, range 43-78 years), and 40% had acute to subacute onset. Clinical manifestations included sensory-motor neuropathy, sensory ataxia caused by proprioceptive impairment, and elevated cerebrospinal fluid protein levels.
The age at onset of CIDP with MN was earlier than that of anti-CNTN1 antibody-associated AN. MN may occur before, after or concurrently with CIDP. The early detection and isotyping of anti-CNTN1 and anti-PLA2R antibodies and the monitoring of isotype switching may be essential for suspected CIDP patients.
先前的文献中已有报道抗接触蛋白 1（CNTN1）抗体相关的慢性炎症性脱髓鞘性多发性神经病（CIDP）与膜性肾病（MN）同时存在。在最新的研究中，针对连接蛋白（paranodal）蛋白自身抗体阳性的 CIDP 被定义为自身免疫性神经节病（AN）。鉴于 CIDP 与 MN 之间的关系尚不明确，我们进行了一项病例研究和文献复习，以探讨伴有 MN 的抗 CNTN 抗体相关 AN 的临床特征。
我们对 1 例临床上表现为 MN 且伴有周围神经病的患者的血液样本进行了神经丝 155（NF155）、神经丝 186（NF186）、CNTN1、CNTN2、接触蛋白相关糖蛋白 1（CASPR1）和磷脂酶 A2 受体（PLA2R）抗体检测，采用双重免疫荧光染色，并通过酶联免疫吸附试验（ELISA）对 PLA2R 抗体 IgG 进行定量测量。通过文献检索，我们检索到抗 CNTN1 抗体相关 AN、抗 CNTN1 抗体相关 AN 伴 MN 和 CIDP 伴 MN 的病例报告，并进行了临床特征的对比分析。根据 CIDP 和 MN 发病的时间顺序对病例进行分组，以比较临床特征。
1 例抗 PLA2R 阳性的 57 岁男性因四肢麻木、无力和本体感觉障碍而入院，诊断为抗 CNTN1 抗体相关 AN，经免疫治疗后恢复良好。我们的文献检索共检索到 22 例 CIDP 伴 MN，这些病例在 CIDP 之前、之后或同时发生。早期单一药物或联合免疫治疗的效果良好，但 22 例 CIDP 伴 MN 中有 8 例最终出现不同的运动后遗症。5 例患者存在抗 CNTN1 抗体相关 AN 伴 MN，其中男性占多数（男：女=4:1），发病年龄较晚（60.2±15.7 岁，范围 43-78 岁），40%为急性至亚急性起病。临床表现包括感觉运动神经病、本体感觉障碍引起的感觉性共济失调和脑脊液蛋白水平升高。
CIDP 伴 MN 的发病年龄早于抗 CNTN1 抗体相关 AN。MN 可发生于 CIDP 之前、之后或与 CIDP 同时发生。早期检测和抗 CNTN1 和抗 PLA2R 抗体的同种型分型以及同种型转换的监测可能对疑似 CIDP 患者至关重要。
