Chen John J, Tobin W Oliver, Majed Masoud, Jitprapaikulsan Jiraporn, Fryer James P, Leavitt Jacqueline A, Flanagan Eoin P, McKeon Andrew, Pittock Sean J
Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.
Department of Neurology, Mayo Clinic, Rochester, Minnesota.
JAMA Ophthalmol. 2018 Apr 1;136(4):419-422. doi: 10.1001/jamaophthalmol.2017.6757.
Autoantibodies to aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) are recently established biomarkers of autoimmune optic neuritis whose frequency and accompanying phenotype, especially for MOG-IgG, are still being characterized. The Optic Neuritis Treatment Trial (ONTT) was a well-known randomized clinical trial in optic neuritis; therefore, knowledge of the serostatus and accompanying phenotype of these patients would be useful to determine the frequency of these antibodies in patients presenting with typical monocular optic neuritis and their outcomes.
To determine the AQP4-IgG and MOG-IgG serostatus of patients within the ONTT and describe the clinical features of seropositive patients.
DESIGN, SETTING, AND PARTICIPANTS: In this follow-up study of the randomized clinical trial, ONTT, conducted between July 1, 1988, and June 30, 1991, analysis of serum for AQP4-IgG and MOG-IgG was performed from January 1 to April 30, 2017. A total of 177 patients from the ONTT with acute optic neuritis and serum available for analysis were enrolled from 13 academic referral centers.
Analysis of serum for AQP4-IgG and MOG-IgG was performed at Mayo Clinic Neuroimmunology Laboratory in 2017 with a flow cytometry, live cell, AQP4- and MOG-transfected cell-based assay.
Aquaporin-4-IgG and MOG-IgG serostatus.
Of the 177 patients in the study (135 women and 42 men; mean [SD] age, 32.8 [6.9] years), 3 were positive for MOG-IgG (1.7%) and none were positive for AQP4-IgG. All 3 patients positive for MOG-IgG had disc edema at presentation. Two patients later had a single episode of recurrent optic neuritis. All 3 patients had complete recovery of visual acuity, and none were corticosteroid dependent, although peripheral visual field loss persisted in 1 patient. None of the 3 patients positive for MOG-IgG had demyelinating lesions on magnetic resonance imaging scans, and none had developed multiple sclerosis at the 15-year follow-up.
Frequency of MOG-IgG was rare in the ONTT, and AQP4-IgG was not found in patients in the ONTT. Characteristics of patients positive for MOG-IgG in the ONTT support the previously described phenotype of MOG-IgG optic neuritis. Myelin oligodendrocyte glycoprotein-related disease appears to be a different entity than multiple sclerosis. Overall, AQP4-IgG and MOG-IgG may be less common in isolated optic neuritis than previously reported.
水通道蛋白4（AQP4）和髓鞘少突胶质细胞糖蛋白（MOG）自身抗体是最近确立的自身免疫性视神经炎生物标志物，其出现频率及伴随的表型，尤其是MOG-IgG的相关情况，仍在研究之中。视神经炎治疗试验（ONTT）是一项著名的视神经炎随机临床试验；因此，了解这些患者的血清状态及伴随表型，对于确定典型单眼视神经炎患者中这些抗体的出现频率及其预后很有帮助。
确定ONTT患者的AQP4-IgG和MOG-IgG血清状态，并描述血清阳性患者的临床特征。
设计、地点和参与者：在这项对1988年7月1日至1991年6月30日进行的随机临床试验ONTT的随访研究中，于2017年1月1日至4月30日对血清进行AQP4-IgG和MOG-IgG分析。从13个学术转诊中心招募了ONTT中177例患有急性视神经炎且有可用血清进行分析的患者。
2017年在梅奥诊所神经免疫学实验室采用流式细胞术、活细胞、基于AQP4和MOG转染细胞的检测方法对血清进行AQP4-IgG和MOG-IgG分析。
水通道蛋白4-IgG和MOG-IgG血清状态。
研究中的177例患者（135例女性和42例男性；平均[标准差]年龄为32.8[6.9]岁），3例MOG-IgG阳性（1.7%），无AQP4-IgG阳性。所有3例MOG-IgG阳性患者就诊时均有视盘水肿。2例患者后来有单次复发性视神经炎发作。所有3例患者视力均完全恢复，且均不依赖皮质类固醇，尽管1例患者仍存在周边视野缺损。3例MOG-IgG阳性患者的磁共振成像扫描均无脱髓鞘病变，在15年随访时均未发生多发性硬化。
ONTT中MOG-IgG出现频率罕见，ONTT患者中未发现AQP4-IgG。ONTT中MOG-IgG阳性患者的特征支持先前描述的MOG-IgG视神经炎表型。髓鞘少突胶质细胞糖蛋白相关疾病似乎是一种不同于多发性硬化的疾病实体。总体而言，AQP4-IgG和MOG-IgG在孤立性视神经炎中的出现可能比先前报道的更为少见。
