Cell-based assays for the detection of MOG antibodies: a comparative study
Cell-based assays for the detection of MOG antibodies: a comparative study
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DOI：
10.1007/s00415-020-10024-0
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发表时间：
2020-07-04
影响因子：
6
通讯作者：
Franciotta, Diego
中科院分区：
文献类型：
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作者：
Gastaldi, Matteo;Scaranzin, Silvia;Franciotta, Diego
背景髓鞘少突胶质细胞糖蛋白（MOG）抗体的检测对于MOG抗体相关疾病（MOGAD）的鉴别诊断和CNS获得性脱髓鞘综合征（MS）的鉴别诊断具有重要意义。我们比较了四种基于细胞的检测（CBA）的诊断性能。方法对204例“可能MOGAD”（55例）、MS（112例）和其他神经系统疾病（OND，37例）患者的血清进行MOG-IgG检测，采用抗重链和轻链二抗的活CBA（LCBA-IgG（H+L））和IgG（1）的活CBA（LCBA-IgG（1））。另外，使用含抗Fc γ二抗的活CBA（LCBA-IgG（Fc γ））和含抗Fc γ二抗的市售固定CBA（FCBA-IgG（Fc γ））对71例患者的亚组进行了检测（.）结果MOG-IgG阳性57例（27.9%）。LCBA-IgG（H+L）的敏感性为89.1%（CI：77.8-95.9），特异性为93.3%（CI：88.0-96.7），LCBA-IgG（1）的敏感性为74.6%（CI：61.0-85.3），特异性为100%（CI：97.6-100）。57份样本中的18份（31%）显示不一致结果（LCBA-IgG均为阴性（1））;其中，3份“可能MOGAD”样本显示高滴度MOG-IgG（>= 1：640）和MOG-IgG阳性（2），而15/18份样本显示低滴度MOG-IgG（1：160/1：320）和混合诊断（5份“可能MOGAD”，6份MS，4份OND）。在亚组分析中，LCBA-IgG（Fc γ）的灵敏度为92.3%（CI：79.1-98.4），特异性为97.0%（CI：83.8-99.9），FCBA-IgG（Fc γ）的灵敏度为87.2%（CI：72.6-95.7），特异性为97.0%（CI：83.8-99.9）。结论LCBA-IgG（1）的特异性最高，但与MOG-IgG（2）的反应性不一致，其意义有待进一步研究。使用LCBA-IgG（H+L）/ IgG（Fc γ）检测的样品滴定对于有意义的结果解读非常重要。在亚组分析中，LCBA-IgG（Fc γ）产生的准确性最高，FCBA-IgG（Fc γ）具有良好的特异性，但存在假阴性结果的风险。
Background The detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) is fundamental for the identification of MOG antibody-associated disorders (MOGAD), and the differential diagnosis of acquired demyelinating syndromes of the CNS, among which multiple sclerosis (MS). We compared the diagnostic performance of four cell-based assays (CBAs) for their detection. Methods Consecutive sera from 204 patients with 'possible MOGAD' (55), MS (112), and other neurological disorders (OND, 37) were tested for MOG-IgG with a live-CBA with anti-heavy-and-light chain secondary-antibody (LCBA-IgG(H+L)), and a live-CBA for IgG(1)(LCBA-IgG(1)). A subgroup of 71 patients was additionally tested with a live-CBA with anti-Fc gamma secondary-antibody (LCBA-IgG(Fc gamma)), and a commercial fixed-CBA with anti-Fc gamma secondary-antibody (FCBA-IgG(Fc gamma))(.) Results Fifty-seven/204 patients (27.9%) were MOG-IgG-positive. Sensitivity was 89.1% (CI:77.8-95.9) and specificity 93.3% (CI:88.0-96.7) for LCBA-IgG(H+L), and 74.6% (CI:61.0-85.3) and 100% (CI:97.6-100) for LCBA-IgG(1). Eighteen of 57 (31%) samples showed discrepant results (all negative on LCBA-IgG(1)); of these, three with 'possible MOGAD' showed high-titer MOG-IgG (>= 1:640), and positivity for MOG-IgG(2), whereas 15/18 had low-titer MOG-IgG (1:160/1:320) and mixed diagnoses (5 'possible MOGAD', 6 MS, 4 OND). In the subgroup analysis, sensitivity was 92.3% (CI:79.1-98.4) and specificity 97.0% (CI:83.8-99.9) for LCBA-IgG(Fc gamma), and 87.2% (CI:72.6-95.7) and 97.0% (CI:83.8-99.9) for FCBA-IgG(Fc gamma). Conclusions LCBA-IgG(1)showed the highest specificity but can miss MOG-IgG(2)reactivities, whose meaning warrants further investigations. Titration of samples tested with LCBA-IgG(H+L)/ IgG(Fc gamma)is important for meaningful interpretation of the results. In the subgroup analysis, LCBA-IgG(Fc gamma)yielded the highest accuracy, and FCBA-IgG(Fc gamma)good specificity, but it was at risk of false-negative results.