Manzano Giovanna S, Salky Rebecca, Mateen Farrah J, Klawiter Eric C, Chitnis Tanuja, Levy Michael, Matiello Marcelo
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Front Neurol. 2022 Jun 20;13:947630. doi: 10.3389/fneur.2022.947630. eCollection 2022.
Myelin oligodendrocyte glycoprotein antibody associated disease (MOG-AD) is a CNS demyelinating disease, typically presenting with optic neuritis, transverse myelitis, and/or ADEM-like syndromes. The positive predictive value (PPV) of MOG-IgG testing by live cell-based assay was reported to be 72% in a study performed at the Mayo Clinic using a cut-off of 1:20. PPV may vary depending upon the tested population, thus supporting further investigation of MOG-IgG testing at other centers. In this real-world institutional cohort study, we determined the PPV of serum MOG-IgG for clinically defined MOG-AD in our patient population. The Massachusetts General Brigham Research Patient Data Registry database was queried for patients with positive serum MOG-IgG detection, at least once, between January 1, 2017 and March 25, 2021. All were tested via the MOG-IgG1 fluorescence-activated cell sorting assay (Mayo Laboratories, Rochester, MN). MOG-IgG positive cases were reviewed for fulfillment of typical MOG-AD clinical features, determined by treating neurologists and study authors. Of 1,877 patients tested, 78 (4.2%) patients tested positive for MOG-IgG with titer ≥1:20, and of these, 67 had validated MOG-AD yielding a PPV of 85.9%. Using a ≥1:40 titer cutoff, 65 (3.5%) tested positive and PPV was 93.8%. Three MOG positive cases had a prototypical multiple sclerosis diagnosis (RRMS = 2, titers 1:20 and 1:40; PPMS = 1; 1:100). The treating diagnosis for one RRMS patient with a 1:40 titer was subsequently modified to MOG-AD by treating neurologists. Validated diagnoses of the remaining positive patients without MOG-AD included: migraine ( = 2, titers 1:20, 1:100), inclusion body myositis ( = 1, titer 1:100), autoimmune encephalitis ( = 2, titers 1:20, 1:20), hypoxic ischemic brain injury ( = 1, titer 1:20), IgG4-related disease ( = 1, titer 1:20), and idiopathic hypertrophic pachymeningitis ( = 1, titer 1:20). In our cohort, the PPV for MOG-IgG improved utilizing a titer cut-off of ≥1:40. The presence of positive cases with and without demyelinating features, emphasizes a need for testing in the appropriate clinical context, analysis of titer value and clinical interpretation.
髓鞘少突胶质细胞糖蛋白抗体相关疾病（MOG-AD）是一种中枢神经系统脱髓鞘疾病，通常表现为视神经炎、横贯性脊髓炎和/或ADEM样综合征。在梅奥诊所进行的一项研究中，使用基于活细胞检测的MOG-IgG检测的阳性预测值（PPV）据报道在截断值为1:20时为72%。PPV可能因测试人群而异，因此支持在其他中心进一步研究MOG-IgG检测。在这项真实世界的机构队列研究中，我们确定了血清MOG-IgG在我们患者群体中对临床定义的MOG-AD的PPV。查询了马萨诸塞州综合布莱根医院研究患者数据登记数据库中在2017年1月1日至2021年3月25日期间至少有一次血清MOG-IgG检测呈阳性的患者。所有患者均通过MOG-IgG1荧光激活细胞分选检测法（梅奥实验室，明尼苏达州罗切斯特）进行检测。由治疗神经科医生和研究作者确定，对MOG-IgG阳性病例进行审查，以确定是否符合典型的MOG-AD临床特征。在1877名接受检测的患者中，78名（4.2%）患者的MOG-IgG检测呈阳性，滴度≥1:20，其中67名经证实患有MOG-AD，PPV为85.9%。使用≥1:40的滴度截断值时，65名（3.5%）检测呈阳性，PPV为93.8%。3例MOG阳性病例被诊断为典型的多发性硬化症（复发缓解型多发性硬化症=2例，滴度分别为1:20和1:40；原发进展型多发性硬化症=1例；1:100）。一名复发缓解型多发性硬化症患者，滴度为1:40，其治疗诊断随后被治疗神经科医生修改为MOG-AD。其余无MOG-AD阳性患者的确诊诊断包括：偏头痛（=2例，滴度分别为1:20、1:100）、包涵体肌炎（=1例，滴度1:100）、自身免疫性脑炎（=2例，滴度分别为1:20、1:20）、缺氧缺血性脑损伤（=1例，滴度1:20）、IgG4相关疾病（=1例，滴度1:20）和特发性肥厚性硬脑膜炎（=1例，滴度1:20）。在我们的队列中，使用≥1:40的滴度截断值时，MOG-IgG的PPV有所提高。存在有和没有脱髓鞘特征的阳性病例，强调了在适当的临床背景下进行检测、分析滴度值和临床解读的必要性。
