Yokoyama Kinya, Maruwaka Mikio, Yoshikawa Kazuhiro, Araki Yoshio, Okamoto Sho, Sumitomo Masaki, Kawamura Akino, Sakamoto Yusuke, Shimizu Kenzo, Izumi Takashi, Wakabayashi Toshihiko
Department of Neurosurgery, Nagoya University Graduate School of Medicine, Aichi, Japan.
Department of Neurosurgery, Nagoya University Graduate School of Medicine, Aichi, Japan.
World Neurosurg. 2018 Jan;109:e446-e459. doi: 10.1016/j.wneu.2017.09.204. Epub 2017 Oct 13.
In moyamoya disease (MMD), the causes of differences in clinical features between children and adults and of the dramatic temporal changes in moyamoya vessels are poorly understood. We previously discovered elevated levels of m/z 4588 and m/z 4473 peptides in cerebrospinal fluid (CSF) in patients with MMD. This study examined the amino acid sequences of these peptides and quantified in specimens.
The m/z 4588 and m/z 4473 peptides in CSF from patients with MMD were purified and concentrated by high-performance liquid chromatography and ultrafiltration. Liquid chromatography coupled with tandem mass spectrometry analysis was performed to identify the amino acid sequences of these peptides. We quantified these peptides in samples using sandwich enzyme-linked immunosorbent assay, and concentrations in CSF were compared between MMD (n = 40, 19 male; median age, 37 years) and non-MMD intracranial disease (n = 40, 19 male; median age, 39 years) as controls.
These peptides were identified as proenkephalin 143-183 (PENK 143-183). The concentration of PENK 143-183 was significantly greater in patients with MMD (median, 8,270 pmol/L) than control patients (median, 3,760 pmol/L; P < 0.001) and decreased in an age-dependent manner in MMD (r = -0.57; P < 0.001). The area under the receiver operating characteristic curve in children (age <18 years) was 0.885 (95% confidence interval 0.741-1). The correlation between proenkephalin concentration and temporal changes in moyamoya vessels was suggested.
Proenkephalin 143-183 in CSF may offer a helpful diagnostic biomarker in pediatric MMD. The effect of enkephalin peptides through opioid growth factor receptor or delta opioid receptor might be associated with the pathophysiology of MMD.
在烟雾病（MMD）中，儿童与成人临床特征差异以及烟雾血管显著的时间变化的原因尚不清楚。我们之前发现MMD患者脑脊液（CSF）中m/z 4588和m/z 4473肽水平升高。本研究检测了这些肽的氨基酸序列并对标本进行定量分析。
采用高效液相色谱和超滤法对MMD患者脑脊液中的m/z 4588和m/z 4473肽进行纯化和浓缩。进行液相色谱-串联质谱分析以鉴定这些肽的氨基酸序列。我们使用夹心酶联免疫吸附测定法对样品中的这些肽进行定量，并比较了MMD患者（n = 40，男性19例；中位年龄37岁）和非MMD颅内疾病患者（n = 40，男性19例；中位年龄39岁）作为对照的脑脊液浓度。
这些肽被鉴定为脑啡肽原143 - 183（PENK 143 - 183）。MMD患者中PENK 143 - 183的浓度（中位数，8270 pmol/L）显著高于对照患者（中位数，3760 pmol/L；P < 0.001），且在MMD中呈年龄依赖性降低（r = -0.57；P < 0.001）。儿童（年龄<18岁）的受试者工作特征曲线下面积为0.885（95%置信区间0.741 - 1）。提示脑啡肽原浓度与烟雾血管的时间变化之间存在相关性。
脑脊液中的脑啡肽原143 - 183可能为儿童烟雾病提供一种有用的诊断生物标志物。脑啡肽肽通过阿片样生长因子受体或δ阿片受体的作用可能与烟雾病的病理生理学相关。
