Nuffield Department of Clinical Neurosciences (P.W., M.W., B.L., M.J., G.T., J.R., J.P., M.I.L., A.V.), John Radcliffe Hospital, Oxford, UK; Department of Neurology (K.C.O.), Yale School of Medicine, New Haven, CT; Clinical Department of Neurology (M.R.), Innsbruck Medical University, Innsbruck, Austria; Department of Neurology (D.K.S., I.N.) and Department of Multiple Sclerosis Therapeutics (T.M., K.F.) Tohoku University School of Medicine, Sendai, Japan; and Department of Neurology (T.T.), Yonezawa National Hospital, Yonezawa, Japan.
Neurol Neuroimmunol Neuroinflamm. 2015 Mar 19;2(3):e89. doi: 10.1212/NXI.0000000000000089. eCollection 2015 Jun.
To optimize sensitivity and disease specificity of a myelin oligodendrocyte glycoprotein (MOG) antibody assay.
Consecutive sera (n = 1,109) sent for aquaporin-4 (AQP4) antibody testing were screened for MOG antibodies (Abs) by cell-based assays using either full-length human MOG (FL-MOG) or the short-length form (SL-MOG). The Abs were initially detected by Alexa Fluor goat anti-human IgG (H + L) and subsequently by Alexa Fluor mouse antibodies to human IgG1.
When tested at 1:20 dilution, 40/1,109 sera were positive for AQP4-Abs, 21 for SL-MOG, and 180 for FL-MOG. Only one of the 40 AQP4-Ab-positive sera was positive for SL-MOG-Abs, but 10 (25%) were positive for FL-MOG-Abs (p = 0.0069). Of equal concern, 48% (42/88) of sera from controls (patients with epilepsy) were positive by FL-MOG assay. However, using an IgG1-specific secondary antibody, only 65/1,109 (5.8%) sera were positive on FL-MOG, and AQP4-Ab- positive and control sera were negative. IgM reactivity accounted for the remaining anti-human IgG (H + L) positivity toward FL-MOG. The clinical diagnoses were obtained in 33 FL-MOG-positive patients, blinded to the antibody data. IgG1-Abs to FL-MOG were associated with optic neuritis (n = 11), AQP4-seronegative neuromyelitis optica spectrum disorder (n = 4), and acute disseminated encephalomyelitis (n = 1). All 7 patients with probable multiple sclerosis (MS) were MOG-IgG1 negative.
The limited disease specificity of FL-MOG-Abs identified using Alexa Fluor goat anti-human IgG (H + L) is due in part to detection of IgM-Abs. Use of the FL-MOG and restricting to IgG1-Abs substantially improves specificity for non-MS demyelinating diseases.
This study provides Class II evidence that the presence of serum IgG1- MOG-Abs in AQP4-Ab-negative patients distinguishes non-MS CNS demyelinating disorders from MS (sensitivity 24%, 95% confidence interval [CI] 9%-45%; specificity 100%, 95% CI 88%-100%).
优化髓鞘少突胶质细胞糖蛋白（MOG）抗体检测的灵敏度和疾病特异性。
连续检测了 1109 份送检的水通道蛋白 4（AQP4）抗体检测血清，通过基于细胞的检测方法用全长人 MOG（FL-MOG）或短长度形式（SL-MOG）进行 MOG 抗体（Abs）筛查。Abs 最初通过 Alexa Fluor 山羊抗人 IgG（H + L）检测，随后通过 Alexa Fluor 小鼠抗人 IgG1 检测。
以 1:20 稀释度检测时，40/1109 份血清 AQP4-Ab 阳性，21 份 SL-MOG 阳性，180 份 FL-MOG 阳性。40 份 AQP4-Ab 阳性血清中只有 1 份为 SL-MOG-Ab 阳性，但 10（25%）份为 FL-MOG-Ab 阳性（p = 0.0069）。同样值得关注的是，88%（42/88）份来自对照组（癫痫患者）的血清通过 FL-MOG 检测呈阳性。然而，使用 IgG1 特异性二级抗体，只有 65/1109（5.8%）份血清在 FL-MOG 上呈阳性，而 AQP4-Ab 阳性和对照血清均为阴性。针对 FL-MOG 的剩余抗人 IgG（H + L）阳性是由 IgM 反应引起的。在 33 名 FL-MOG 阳性患者中获得了临床诊断，这些患者的诊断结果对抗体数据进行了盲法评估。FL-MOG 的 IgG1-Abs 与视神经炎（n = 11）、AQP4 阴性的视神经脊髓炎谱系障碍（n = 4）和急性播散性脑脊髓炎（n = 1）相关。所有 7 名可能患有多发性硬化症（MS）的患者均为 MOG-IgG1 阴性。
使用 Alexa Fluor 山羊抗人 IgG（H + L）检测到的 FL-MOG-Abs 的有限疾病特异性部分归因于 IgM-Abs 的检测。使用 FL-MOG 并限制为 IgG1-Abs 可大大提高非 MS 脱髓鞘疾病的特异性。
本研究提供了 II 级证据，表明在 AQP4-Ab 阴性患者中存在血清 IgG1-MOG-Abs 可将非 MS 中枢神经系统脱髓鞘疾病与 MS 区分开来（敏感性 24%，95%置信区间[CI] 9%-45%；特异性 100%，95% CI 88%-100%）。
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