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Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis
Ophthalmology ( IF 13.7 ) Pub Date : 2018-04-30 , DOI: 10.1016/j.ophtha.2018.03.041
Jiraporn Jitprapaikulsan , John J. Chen , Eoin P. Flanagan , W. Oliver Tobin , Jim P. Fryer , Brian G. Weinshenker , Andrew McKeon , Vanda A. Lennon , Jacqueline A. Leavitt , Jan-Mendelt Tillema , Claudia Lucchinetti , B. Mark Keegan , Orhun Kantarci , Cheryl Khanna , Sarah M. Jenkins , Grant M. Spears , Jessica Sagan , Sean J. Pittock

Purpose

To determine the aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG) serostatus and visual outcomes in patients with recurrent optic neuritis (rON) initially seeking treatment.

Design

Cross-sectional cohort study.

Participants

The study identified patients by searching the Mayo Clinic computerized central diagnostic index (January 2000–March 2017). The 246 eligible patients fulfilled the following criteria: (1) initially seeking treatment for at least 2 consecutive episodes of optic neuritis (ON) and (2) serum available for testing.

Methods

Serum was tested for aquaporin-4 IgG and MOG IgG1 using an in-house validated flow cytometric assay using live HEK293 cells transfected with M1 aquaporin-4 or full-length MOG.

Main Outcomes Measures

Aquaporin-4 IgG and MOG IgG1 serostatus, clinical characteristics, and visual outcomes.

Results

Among 246 patients with rON at presentation, glial autoantibodies were detected in 32% (aquaporin-4 IgG, 19%; MOG IgG1, 13%); 186 patients had rON only and 60 patients had rON with subsequent additional inflammatory demyelinating attacks (rON-plus group). The rON-only cohort comprised the following: double seronegative (idiopathic), 110 patients (59%); MOG IgG1 positive, 27 patients (15%; 4 with chronic relapsing inflammatory optic neuropathy); multiple sclerosis (MS), 25 patients (13%); and aquaporin-4 IgG positive, 24 patients (13%). The rON-plus cohort comprised the following: aquaporin-4 IgG positive, 23 patients (38%); MS, 22 patients (37%); double seronegative, 11 patients (18%); and MOG IgG1 positive, 4 patients (7%). The annualized relapse rate for the rON-only group was 1.2 for MOG IgG1−positive patients, 0.7 for double-seronegative patients, 0.6 for aquaporin-4 IgG−positive patients, and 0.4 for MS patients (P = 0.005). The median visual acuity (VA) of patients with the worst rON-only attack at nadir were hand movements in aquaporin-4 IgG−positive patients, between counting fingers and hand movements in MOG IgG1−positive patients, 20/800 in idiopathic patients, and 20/100 in MS patients (P = 0.02). The median VA at last follow-up for affected eyes of the rON-only cohort were counting fingers for aquaporin-4 IgG−positive patients, 20/40 for idiopathic patients, 20/25 for MS patients and MOG IgG1−positive patients (P = 0.006). At 5 years after ON onset, 59% of aquaporin-4 IgG−positive patients, 22% of idiopathic patients, 12% of MOG IgG1−positive patients, and 8% of MS patients were estimated to have severe visual loss.

Conclusions

Glial autoantibodies (MOG IgG1 or aquaporin-4 IgG) are found in one third of all patients with rON. Aquaporin-4 IgG seropositivity predicts a worse visual outcome than MOG IgG1 seropositivity, double seronegativity, or MS diagnosis. Myelin oligodendrocyte glycoprotein IgG1 is associated with a greater relapse rate but better visual outcomes.



中文翻译:

Aquaporin-4和髓磷脂少突胶质糖蛋白自身抗体状态可预测复发性视神经炎的结果

目的

为了确定最初寻求治疗的复发性视神经炎(rON)患者的aquaporin-4和髓鞘少突胶质细胞糖蛋白(MOG)免疫球蛋白G(IgG)血清状况和视觉结果。

设计

横断面队列研究。

参加者

该研究通过搜索Mayo Clinic计算机化中央诊断指标(2000年1月至2017年3月)来识别患者。246名符合条件的患者符合以下标准:(1)最初寻求连续治疗至少2次连续性视神经炎(ON)的治疗,以及(2)可用于测试的血清。

方法

使用内部验证的流式细胞术,使用转染了M1 Aquaporin-4或全长MOG的活HEK293细胞,对血清中的Aquaporin-4 IgG和MOG IgG1进行了测试。

主要结果指标

Aquaporin-4 IgG和MOG IgG1血清状态,临床特征和视觉结果。

结果

在246位出现rON的患者中,神经胶质自身抗体检出率为32%(aquaporin-4 IgG,19%; MOG IgG1,13%);186例患者仅接受rON,60例患者接受rON并随后发生其他炎症性脱髓鞘性发作(rON-plus组)。仅rON的队列包括:双重血清阴性(特发性)110例(59%);MOG IgG1阳性,27例(15%; 4例慢性复发性炎症性视神经病变);多发性硬化症(MS),25例(13%); 和Aquaporin-4 IgG阳性的24例患者(13%)。rON-plus队列包括:aquaporin-4 IgG阳性,23例(38%);MS,22例患者(37%);双血清阴性,11例(18%); MOG IgG1阳性,4例(7%)。对于MOG IgG1阳性的患者,仅rON组的年复发率是1.2,为0。P  = 0.005)。在最低点,rON发作最严重的患者的中位视力(VA)是aquaporin-4 IgG阳性患者的手部动作,MOG IgG1阳性患者的手指数与手部动作之间,特发性患者为20/800, MS患者中为20/100(P  = 0.02)。仅rON队列的患儿最近一次随访的中位VA为aquaporin-4 IgG阳性患者计数手指,特发性患者为20/40,MS患者和MOG IgG1阳性患者为20/25(P  = 0.006)。发病5年后,估计有59%的Aquaporin-4 IgG阳性患者,22%的特发性患者,12%的MOG IgG1阳性患者和8%的MS患者患有严重的视力丧失。

结论

在所有rON患者中,有三分之一发现了神经胶质自身抗体(MOG IgG1或aquaporin-4 IgG)。与MOG IgG1血清反应阳性,双重血清阴性反应或MS诊断相比,Aquaporin-4 IgG血清反应阳性预示着较差的视觉效果。髓磷脂少突胶质细胞糖蛋白IgG1与较高的复发率但具有较好的视觉效果有关。

更新日期:2018-04-30
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