Peripheral Neuropathy Research Center, Dong-A University College of Medicine, Busan, Republic of Korea.
Department of Neurology, Dong-A University College of Medicine, Busan, Republic of Korea.
Eur J Neurol. 2023 Jun;30(6):1745-1754. doi: 10.1111/ene.15763. Epub 2023 Mar 15.
Elevated plasma concentrations of neural cell adhesion molecule 1 (NCAM1) and p75 neurotrophin receptor (p75) in patients with peripheral neuropathy have been reported. This study aimed to determine the specificity of plasma concentration elevation of either NCAM1 or p75 in a subtype of Charcot-Marie-Tooth disease (CMT) and its correlation with pathologic nerve status and disease severity.
Blood samples were collected from 138 patients with inherited peripheral neuropathy and 51 healthy controls. Disease severity was measured using Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNSv2), and plasma concentrations of NCAM1 and p75 were analyzed by enzyme-linked immunosorbent assay. Eight sural nerves from CMT patients were examined to determine the relation of histopathology and plasma NCAM1 levels.
Plasma concentration of NCAM1, but not p75, was specifically increased in demyelinating subtypes of CMT (median = 7100 pg/mL, p < 0.001), including CMT1A, but not in axonal subtype (5964 pg/mL, p > 0.05), compared to the control (3859 pg/mL). CMT1A patients with mild or moderate severity (CMTNSv2 < 20) showed higher levels of plasma NCAM1 than healthy controls. Immunofluorescent NCAM1 staining for the sural nerves of CMT patients showed that NCAM1-positive onion bulb cells and possible demyelinating Schwann cells might be associated with the specific increase of plasma NCAM1 in demyelinating CMT.
The plasma NCAM1 levels in demyelinating CMT might be a surrogate biomarker reflecting pathological Schwann cell status and disease progression.
有报道称，周围神经病变患者的血浆神经细胞黏附分子 1（NCAM1）和 p75 神经营养因子受体（p75）浓度升高。本研究旨在确定在一种夏科-马里-图什病（CMT）亚型中，NCAM1 或 p75 的血浆浓度升高是否具有特异性，以及其与病理神经状况和疾病严重程度的相关性。
收集了 138 例遗传性周围神经病患者和 51 名健康对照者的血样。采用夏科-马里-图什神经病评分 2 版（CMTNSv2）测量疾病严重程度，并通过酶联免疫吸附试验分析 NCAM1 和 p75 的血浆浓度。检查 8 例 CMT 患者的腓肠神经，以确定组织病理学与血浆 NCAM1 水平的关系。
与对照组（3859pg/ml）相比，脱髓鞘型 CMT（包括 CMT1A 型）患者的血浆 NCAM1 浓度（中位数=7100pg/ml，p<0.001），但 p75 浓度无明显升高（5964pg/ml，p>0.05）。CMT1A 患者中病情较轻或中度（CMTNSv2<20）的患者，其血浆 NCAM1 水平高于健康对照组。CMT 患者腓肠神经的免疫荧光 NCAM1 染色显示，NCAM1 阳性的洋葱球细胞和可能的脱髓鞘 Schwann 细胞可能与脱髓鞘 CMT 中血浆 NCAM1 的特异性升高有关。
脱髓鞘 CMT 患者的血浆 NCAM1 水平可能是反映病理 Schwann 细胞状态和疾病进展的替代生物标志物。
