Giannoccaro Maria Pia, Waters Patrick, Pizza Fabio, Liguori Rocco, Plazzi Giuseppe, Vincent Angela
Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, United Kingdom.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Sleep. 2017 Feb 1;40(2). doi: 10.1093/sleep/zsw056.
Recently, antibodies to the hypocretin receptor 2 (HCRTR2-Abs) were reported in a high proportion of narcolepsy patients who developed the disease following Pandemrix® vaccination. We tested a group of narcolepsy patients for the HCRTR2-Abs using a newly established cell-based assay.
Sera from 50 narcolepsy type 1 (NT1) and 11 narcolepsy type 2 (NT2) patients, 22 patients with other sleep disorders, 15 healthy controls, and 93 disease controls were studied. Cerebrospinal fluid (CSFs) from three narcoleptic patients were subsequently included. Human embryonic kidney cells were transiently transfected with human HCRTR2, incubated with patients' sera for 1 hr at 1:20 dilution and then fixed. Binding of antibodies was detected by fluorescently labeled secondary antibodies to human immunoglobulin G (IgG) and the different IgG subclasses. A nonlinear visual scoring system was used from 0 to 4; samples scoring ≥1 were considered positive.
Only 3 (5%) of 61 patients showed a score ≥1, one with IgG1- and two with IgG3-antibodies, but titers were low (1:40-1:100). CSFs from these patients were negative. The three positive patients included one NT1 case with associated psychotic features, one NT2 patient, and an NT1 patient with normal hypocretin CSF levels.
Low levels of IgG1 or IgG3 antibodies against HCRTR2 were found in 3 of 61 patients with narcolepsy, although only 1 presented with full-blown NT1. HCRTR2-Abs are not common in narcolepsy unrelated to vaccination.
最近，在接种Pandemrix®疫苗后发病的大部分发作性睡病患者中，发现了针对下丘脑分泌素受体2的抗体（HCRTR2-Abs）。我们使用新建立的基于细胞的检测方法，对一组发作性睡病患者进行了HCRTR2-Abs检测。
研究了来自50例1型发作性睡病（NT1）患者、11例2型发作性睡病（NT2）患者、22例其他睡眠障碍患者、15名健康对照者以及93名疾病对照者的血清。随后纳入了3例发作性睡病患者的脑脊液（CSF）。将人胚胎肾细胞用人类HCRTR2进行瞬时转染，与患者血清按1:20稀释孵育1小时，然后固定。通过荧光标记的抗人免疫球蛋白G（IgG）及不同IgG亚类的二抗检测抗体结合情况。使用0至4的非线性视觉评分系统；评分≥1的样本被视为阳性。
61例患者中仅有3例（5%）评分≥1，1例为IgG1抗体阳性，2例为IgG3抗体阳性，但滴度较低（1:40 - 1:100）。这些患者的脑脊液检测为阴性。3例阳性患者包括1例伴有精神病性特征的NT1患者、1例NT2患者以及1例脑脊液下丘脑分泌素水平正常的NT1患者。
61例发作性睡病患者中有3例发现了低水平的抗HCRTR2的IgG1或IgG3抗体，尽管只有1例表现为典型的NT1。HCRTR2-Abs在与疫苗接种无关的发作性睡病中并不常见。
