Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Institute of Clinical Neuroimmunology, University Hospital and Biomedical Center, Ludwig-Maximilians University Munich, Munich, Germany.
J Neuroinflammation. 2020 Sep 3;17(1):261. doi: 10.1186/s12974-020-01824-2.
New-generation cell-based assays have demonstrated a robust association of serum autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis, and brainstem encephalitis, as well as with neuromyelitis optica (NMO)-like or acute-disseminated encephalomyelitis (ADEM)-like presentations. However, only limited data are yet available on cerebrospinal fluid (CSF) findings in MOG-IgG-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD).
To describe systematically the CSF profile in MOG-EM.
Cytological and biochemical findings (including white cell counts and differentiation; frequency and patterns of oligoclonal bands; IgG/IgM/IgA and albumin concentrations and CSF/serum ratios; intrathecal IgG/IgA/IgM fractions; locally produced IgG/IgM/IgA concentrations; immunoglobulin class patterns; IgG/IgA/IgM reibergrams; Link index; measles/rubella/zoster (MRZ) reaction; other anti-viral and anti-bacterial antibody indices; CSF total protein; CSF L-lactate) from 163 lumbar punctures in 100 adult patients of mainly Caucasian descent with MOG-EM were analyzed retrospectively.
Most strikingly, CSF-restricted oligoclonal IgG bands, a hallmark of multiple sclerosis (MS), were absent in almost 90% of samples (N = 151), and the MRZ reaction, the most specific laboratory marker of MS known so far, in 100% (N = 62). If present, intrathecal IgG (and, more rarely, IgM) synthesis was low, often transient and mostly restricted to acute attacks. CSF WCC was elevated in > 50% of samples (median 31 cells/μl; mostly lymphocytes and monocytes; > 100/μl in 12%). Neutrophils were present in > 40% of samples; activated lymphocytes were found less frequently and eosinophils and/or plasma cells only very rarely (< 4%). Blood-CSF barrier dysfunction (as indicated by an elevated albumin CSF/serum ratio) was present in 48% of all samples and at least once in 55% of all patients (N = 88) tested. The frequency and degree of CSF alterations were significantly higher in patients with acute myelitis than in patients with acute ON and varied strongly depending on attack severity. CSF L-lactate levels correlated significantly with the spinal cord lesion load in patients with acute myelitis (p < 0.0001). Like pleocytosis, blood-CSF barrier dysfunction was present also during remission in a substantial number of patients.
MOG-IgG-positive EM is characterized by CSF features that are distinct from those in MS. Our findings are important for the differential diagnosis of MS and MOG-EM and add to the understanding of the immunopathogenesis of this newly described autoimmune disease.
新一代基于细胞的检测方法已经证明，血清自身抗体与全长人髓鞘少突胶质细胞糖蛋白（MOG-IgG）与（主要是复发性）视神经炎、脊髓炎和脑干脑炎，以及视神经脊髓炎（NMO）样或急性播散性脑脊髓炎（ADEM）样表现之间存在较强的关联。然而，关于 MOG-IgG 相关脑炎（MOG-EM；也称为 MOG 抗体相关疾病，MOGAD）的脑脊液（CSF）发现，目前仅有有限的数据。
系统描述 MOG-EM 的 CSF 特征。
回顾性分析了 100 例主要为白种人成年患者的 163 次腰椎穿刺的细胞学和生化发现（包括白细胞计数和分类；寡克隆带的频率和模式；IgG/IgM/IgA 和白蛋白浓度及 CSF/血清比值；鞘内 IgG/IgA/IgM 分数；局部产生的 IgG/IgM/IgA 浓度；免疫球蛋白类模式；IgG/IgA/IgM 再吸印图谱；Link 指数；麻疹/风疹/带状孢疹（MRZ）反应；其他抗病毒和抗细菌抗体指数；CSF 总蛋白；CSF L-乳酸）。
最显著的是，几乎 90%（N=151）的样本中缺乏 CSF 限制的寡克隆 IgG 带，这是多发性硬化症（MS）的一个标志，而目前已知的最特异的 MS 实验室标志物 MRZ 反应在 100%（N=62）的样本中均为阳性。如果存在，鞘内 IgG（以及更罕见的 IgM）合成较低，通常是短暂的，主要局限于急性发作。>50%的样本中 CSF WCC 升高（中位数为 31 个细胞/μl；主要是淋巴细胞和单核细胞；>100/μl 占 12%）。>40%的样本中存在中性粒细胞；较少发现活化的淋巴细胞，而嗜酸性粒细胞和/或浆细胞则非常罕见（<4%）。48%的所有样本均存在血脑屏障功能障碍（以白蛋白 CSF/血清比值升高为指标），55%（N=88）的所有患者至少有一次出现该功能障碍。与急性视神经炎患者相比，急性脊髓炎患者的 CSF 改变频率和程度明显更高，且严重程度波动较大。急性脊髓炎患者的 CSF L-乳酸水平与脊髓病变负荷显著相关（p<0.0001）。与白细胞增多一样，血脑屏障功能障碍在相当数量的患者缓解期也存在。
MOG-IgG 阳性的 EM 以与 MS 不同的 CSF 特征为特征。我们的发现对 MS 和 MOG-EM 的鉴别诊断很重要，并有助于理解这种新描述的自身免疫性疾病的免疫发病机制。
