Diagnostic implications of MOG-IgG detection in sera and cerebrospinal fluids
Diagnostic implications of MOG-IgG detection in sera and cerebrospinal fluids
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DOI：
10.1093/brain/awad122
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发表时间：
2023-04-15
期刊：
影响因子：
14.5
通讯作者：
Aoki, Masashi
中科院分区：
文献类型：
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作者：
Matsumoto, Yuki;Kaneko, Kimihiko;Aoki, Masashi
MOG-IgG相关疾病（MOGAD）的谱包括视神经炎（ON）、肌萎缩症（MY）、急性播散性脑脊髓炎（ADEM）、脑干脑炎、大脑皮质脑炎（CE）和AQP 4-IgG阴性视神经肌萎缩症谱障碍（NMOSD）。在MOGAD中，MOG-IgG通常在血清中检测到（MOG-IgG（血清）），但也有一些血清阴性的MOGAD病例在CSF中检测到MOG-IgG（CSF），其诊断意义尚不清楚。在这项横断面研究中，我们确定了来自日本各地的配对血清和CSF用于检测MOG-IgG的患者。两名对MOG-IgG状态不知情的研究者根据目前的建议将其归类为疑似MOGAD（ADEM、CE、NMOSD、ON、MY和其他）或非MOGAD。用连续2倍稀释液评估MOG-IgG（血清）和MOG-IgG（CSF）滴度，以确定终点滴度[血清中>= 1：128和CSF中>= 1：1（未稀释）视为阳性]。用多元回归分析MOG-IgG（血清）、MOG-IgG（脑脊液）与表型的关系。治疗前共检测了671例患者[405例疑似MOGAD，99例多发性硬化，48例AQP 4-IgG阳性NMOSD和119例其他神经系统疾病（OND）]。在疑似MOGAD中，133例患者（33%）血清和/或CSF中MOG-IgG检测阳性; 94例（23%）双阳性（ADEM 36，CE 15，MY 8，NMOSD 9，ON 15和其他11）; 17血清限制性抗体阳性（ADEM 2例，CE 0例，MY 3例，NMOSD 3例，ON 5例，其他4例）22例（4.2%），脑脊液限制性抗体阳性（ADEM 3例，CE 4例，MY 6例，NMOSD 2例，ON 0例，其他7例）22例（5.4%）。AQP 4-IgG阳性的NMOSD、多发性硬化或OND病例均未检测到MOG-IgG（血清）阳性，但2例多发性硬化病例为MOG-IgG（CSF）阳性; MOG-IgG（血清）和MOG-IgG（CSF）在疑似MOGAD中的特异性分别为100% [95%置信区间（CI）99-100%]和99%（95% CI 97-100%）。与AQP 4-IgG阳性NMOSD不同，MOGAD中MOG-IgG（血清）和MOG-IgG（CSF）滴度之间的相关性较弱。多因素回归分析显示MOG-IgG（血清）与ON和ADEM相关，而MOG-IgG（脑脊液）与ADEM和CE相关。诊断另外一例MOGAD病例所需的MOG-IgG（CSF）检测数量为13.3例（ADEM为14.3例，CE为2例，NMOSD为19.5例，ON为无穷大，MY为18.5例，其他为6.1例）。在MOG-IgG（血清/CSF）状态方面，大多数病例为双阳性，同时包括血清限制性（13%）或CSF限制性（17%）病例。这些状态与临床表型独立相关，特别是在血清中ON和CSF中CE的患者中，提示了病理生理学意义和优先诊断检测的实用性。进一步的研究是必要的，以推断区室化MOG-IgG的临床和病理意义。
The spectrum of MOG-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE) and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgG(SERUM)), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgG(CSF)), and its diagnostic implications remains unclear. In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgG(SERUM) and MOG-IgG(CSF) titres were assessed with serial 2-fold dilutions to determine end point titres [>= 1:128 in serum and >= 1:1 (no dilution) in CSF were considered positive]. We analysed the relationship between MOG-IgG(SERUM), MOG-IgG(CSF) and the phenotypes with multivariable regression. A total of 671 patients were tested [405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD and 119 with other neurological diseases (OND)] before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15 and Others 11); 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5 and Others 4); and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0 and Others 7). None of AQP4-IgG-positive NMOSD, multiple sclerosis or OND cases tested positive for MOG-IgG(SERUM), but two with multiple sclerosis cases were MOG-IgG(CSF)-positive; the specificities of MOG-IgG(SERUM) and MOG-IgG(CSF) in suspected MOGAD were 100% [95% confidence interval (CI) 99-100%] and 99% (95% CI 97-100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgG(SERUM) and MOG-IgG(CSF) titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgG(SERUM) was associated with ON and ADEM, whereas MOG-IgG(CSF) was associated with ADEM and CE. The number needed to test for MOG-IgG(CSF) to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY and 6.1 for Others). In terms of MOG-IgG(SERUM/CSF) status, most cases were double-positive while including either serum-restricted (13%) or CSF-restricted (17%) cases. These statuses were independently associated with clinical phenotypes, especially in those with ON in serum and CE in CSF, suggesting pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted to deduce the clinical and pathological significance of compartmentalized MOG-IgG.