儿童获得性脱髓鞘综合征中 MOG 抗体的时间动态变化。
Temporal Dynamics of MOG Antibodies in Children With Acquired Demyelinating Syndrome.
机构信息
From the Department of Pediatric Neurology (E.M.W.), Olgahospital/Klinikum Stuttgart; Department of Pediatric Neurology (H.S.T., A. Bertolini, K.R.), Witten/Herdecke University, Datteln, Germany; Department of Pediatric I (M. Baumann, C.L.), Pediatric Neurology, Medical University of Innsbruck, Innsbruck, Austria; LMU Klinikum (A. Blaschek), Hauner Children´s Hospital, Munich; Division of Pediatric Neurology (A.M.), Department of Pediatrics, Medical University of Leipzig; Department of General Pediatrics (M.K.), Neonatology and Pediatric Cardiology, University Childrens Hospital, Heinrich-Heine- University Duesseldorf, Germany; Department of Neurology (B.K.), Medical University Vienna, Austria; Department of Neurology (D.P.), Children's Hospital of Eastern Ontario, University of Ottawa, Canada; Department of Neuropediatrics (M.P.), Children's Hospital DRK Siegen, Germany; Clinical Department of Neurology (K.S., M.R.), Medical University of Innsbruck, Austria; Division of Pediatric Neurology (M. Schimmel), Childrens Hospital, Medical University of Augsburg; Department of Neuropediatrics and Social Pediatrics (C.T.), University Hospital for Children and Adolescent Medicine, Ruhr-University Bochum; Division of Neuropediatrics and Social Pediatrics (S.W.), Childrens Hospital, Cologne; Division of Pediatric Neurology (G.W.), Department of Pediatrics, Asklepios Klinik Nord, Heidberg, Germany; Department of Pediatric Neurology (B.A.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Pediatrics (N.B.), University Hospital Zagreb, Medical University Zagreb, Croatia; Department of Pediatric Neurology (C.B.), Kinderkrankenhaus St. Marien gGmbH, Landshut, Germany; Division of Pediatric Pulmonology (M. Breu), Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna; Department of Pediatric Neurology (P.B.), Ostschweizer Kinderspital, St. Gallen, Switzerland; Department of Pediatric Neurology (A.D.M.), Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Duisburg-Essen; Department of Pediatric Neurology (K.D.), Children's Hospital Kassel; Department of Neuropediatrics and Muscle Disorders (M.E.), Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; Department of Paediatrics and Adolescent Medicine (A.E.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Department of Pediatric and Adolescent Medicine (M.F.), Medical University Vienna, Austria; Department of Pediatrics (U.G.-S.), LKH Medical University Graz, Austria; Department of Pediatric Neurology (A.H.), University Children's Hospital, University of Zurich; Zentrum für Kinderneurologie AG (T.I.), Zurich, Schwitzerland; Charité Universitätsmedizin Berlin (E.K.), Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Neurology, Germany; Department of Pediatrics (J.K.), Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), Salzburg, Austria; Division of Pediatric Neurology (G.K.), Department of Pediatrics, Caritas-Hospital Bad Mergentheim, Germany; Department of Pediatrics and Adolescent Medicine (S.L.), Hospital Dritter Orden, Munich, Germany; Department of Pediatric Neurology (G.L.), Children's Hospital Altona, Hamburg, Germany; Paediatric Neurology and Neurophysiology Unit (M.N., S.S.), Department of Women's and Children's Health, University Hospital of Padova, Italy; Neuroimmunology Group (M.N., S.S.), Paediatric Research Institute "Città della Speranza," Padova, Italy; Department of Neuropediatrics and Muscle Disorders (A.P.), University Medical Center, Faculty of Medicine, University of Freiburg, Germany; Medical University of Vienna (E.R.-F.), Department of Pediatrics; Department of Neuropediatrics (E.R.-F.), St. Anna Children`s Hospital; Department of Social Medicine (D.R.), Donauspital, Vienna, Austria; Department of Pediatrics (M. Salandin), Division of Pediatric Neurology, Hospital Bozen, Italy; Department of Pediatrics (J.-U.S.), Division of Pediatric Neurology, Gemeinschaftskrankenhaus Herdecke, Medical University Witten, Herdecke, Germany; Department of Pediatrics (J. Stoffels), Division of Neuropediatrics, KJF Klinikum Josefinum, Augsburg, Germany; Neurology Department of Children's University Hospital (J. Strautmanis), Riga Stradins University, Riga, Latvia; Center for Pediatric and Teenage Health Care (D.T.), Child Neurology, Sankt Augustin, Germany; Department of Neuropediatrics (V.T.), University Hospital Carl Gustav Carus, Technische Universität Dresden; and Department of Pediatric Neurology (N.U.), Children's Hospital, Medical University Greifswald, Germany.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2022 Oct 13;9(6). doi: 10.1212/NXI.0000000000200035. Print 2022 Nov.
BACKGROUND AND OBJECTIVE
The spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) comprises monophasic diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), and transverse myelitis and relapsing courses of these presentations. Persistently high MOG antibodies (MOG immunoglobulin G [IgG]) are found in patients with a relapsing disease course. Prognostic factors to determine the clinical course of children with a first MOGAD are still lacking. The objective of the study is to assess the clinical and laboratory prognostic parameters for a risk of relapse and the temporal dynamics of MOG-IgG titers in children with MOGAD in correlation with clinical presentation and disease course.
METHODS
In this prospective multicenter hospital-based study, children with a first demyelinating attack and complete data set comprising clinical and radiologic findings, MOG-IgG titer at onset, and clinical and serologic follow-up data were included. Serum samples were analyzed by live cell-based assay, and a titer level of ≥1:160 was classified as MOG-IgG-positive.
RESULTS
One hundred sixteen children (f:m = 57:59) with MOGAD were included and initially diagnosed with ADEM (n = 59), unilateral ON (n = 12), bilateral ON (n = 16), myelitis (n = 6), neuromyelitis optica spectrum disorder (n = 8) or encephalitis (n = 6). The median follow-up time was 3 years in monophasic and 5 years in relapsing patients. There was no significant association between disease course and MOG-IgG titers at onset, sex, age at presentation, or clinical phenotype. Seroconversion to MOG-IgG-negative within 2 years of the initial event showed a significant risk reduction for a relapsing disease course. Forty-two/one hundred sixteen patients (monophasic n = 26, relapsing n = 16) had serial MOG-IgG testing in years 1 and 2 after the initial event. In contrast to relapsing patients, monophasic patients showed a significant decrease of MOG-IgG titers during the first and second years, often with seroconversion to negative titers. During the follow-up, MOG-IgG titers were persistently higher in relapsing than in monophasic patients. Decrease in MOG-IgG of ≥3 dilution steps after the first and second years was shown to be associated with a decreased risk of relapses. In our cohort, no patient experienced a relapse after seroconversion to MOG-IgG-negative.
DISCUSSION
In this study, patients with declining MOG-IgG titers, particularly those with seroconversion to MOG-IgG-negative, are shown to have a significantly reduced relapse risk.
背景与目的
髓鞘少突胶质细胞糖蛋白（MOG）抗体相关性疾病（MOGAD）的谱包括单相疾病，如急性播散性脑脊髓炎（ADEM）、视神经炎（ON）和横贯性脊髓炎，以及这些表现的复发病程。在复发病程的患者中持续存在高 MOG 抗体（MOG 免疫球蛋白 G [IgG]）。目前仍缺乏预测儿童首次 MOGAD 临床病程的预后因素。本研究的目的是评估儿童 MOGAD 患者复发风险的临床和实验室预后参数，以及 MOG-IgG 滴度与临床表现和疾病病程的时间动态关系。
方法
在这项前瞻性多中心医院基础研究中，纳入了首次脱髓鞘发作且具有完整临床和影像学发现、发病时 MOG-IgG 滴度以及临床和血清学随访数据的儿童。通过活细胞测定法分析血清样本，将滴度水平≥1:160 分类为 MOG-IgG 阳性。
结果
纳入了 116 例 MOGAD 患儿（女性：男性=57:59），最初诊断为 ADEM（n=59）、单侧 ON（n=12）、双侧 ON（n=16）、脊髓炎（n=6）、视神经脊髓炎谱系障碍（n=8）或脑炎（n=6）。在单相患者中，中位随访时间为 3 年，在复发患者中为 5 年。疾病病程与发病时的 MOG-IgG 滴度、性别、发病年龄或临床表型之间无显著关联。在初始事件后 2 年内血清转阴性与复发病程的显著降低风险相关。116 例患者中有 42/116 例（单相 n=26，复发 n=16）在初始事件后 1 年和 2 年进行了 MOG-IgG 连续检测。与复发患者相比，单相患者在第 1 年和第 2 年 MOG-IgG 滴度显著下降，常转为阴性滴度。在随访期间，复发患者的 MOG-IgG 滴度持续高于单相患者。在第 1 年和第 2 年 MOG-IgG 滴度下降≥3 个稀释度与复发风险降低相关。在本队列中，无患者在转为 MOG-IgG 阴性后复发。
讨论
在本研究中，显示 MOG-IgG 滴度下降的患者，尤其是转为 MOG-IgG 阴性的患者，复发风险显著降低。
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