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 IgG₁ (LCBA-IgG₁). A subgroup of 71 patients was additionally tested with a live-CBA with anti-Fcγ secondary-antibody (LCBA-IgG_Fcγ), and a commercial fixed-CBA with anti-Fcγ secondary-antibody (FCBA-IgG_Fcγ)_.

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-IgG₁. Eighteen of 57 (31%) samples showed discrepant results (all negative on LCBA-IgG₁); of these, three with ‘possible MOGAD’ showed high-titer MOG-IgG (≥ 1:640), and positivity for MOG-IgG₂, 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_Fcγ, and 87.2% (CI:72.6–95.7) and 97.0% (CI:83.8–99.9) for FCBA-IgG_Fcγ.

Conclusions

LCBA-IgG₁ showed the highest specificity but can miss MOG-IgG₂ reactivities, whose meaning warrants further investigations. Titration of samples tested with LCBA-IgG_H+L/ IgG_Fcγ is important for meaningful interpretation of the results. In the subgroup analysis, LCBA-IgG_Fcγ yielded the highest accuracy, and FCBA-IgG_Fcγ good specificity, but it was at risk of false-negative results.

中文翻译：

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基于细胞的MOG抗体检测方法：一项比较研究。

背景

髓鞘少突胶质细胞糖蛋白（MOG）抗体的检测对于识别MOG抗体相关疾病（MOGAD）和中枢神经系统获得性脱髓鞘综合征（其中包括多发性硬化症）的鉴别诊断至关重要。我们比较了四种基于细胞的检测（CBA）的诊断性能。

方法

测试了204例“可能的MOGAD”（55），MS（112）和其他神经系统疾病（OND，37）患者的连续血清中含有活CBA的MOG-IgG，以及抗重链和轻链次级抗体抗体（LCBA-IgG _{H + L}）和IgG ₁的活CBA （LCBA-IgG ₁）。亚组71位患者另外接受了带有抗Fcγ二级抗体的活CBA（LCBA- _IgGFcγ）和带有抗Fcγ二级抗体的商业固定CBA（FCBA- _IgGFcγ）的测试_。

结果

204名患者中有57名（27.9％）为MOG-IgG阳性。对LCBA-IgG _{H + L的}敏感性为89.1％（CI：77.8-95.9）和特异性93.3％（CI：88.0-96.7），分别为74.6％（CI：61.0-85.3）和100％（CI：97.6-100）用于LCBA-IgG ₁。57个样本中有18个（31％）显示出不一致的结果（所有LCBA-IgG ₁均为阴性）。其中三个具有“可能的MOGAD”表现出高滴度的MOG-IgG（≥1：640），且对MOG-IgG _2呈阳性，而15/18具有低滴度的MOG-IgG（1：160/1：320） ）和混合诊断（5个“可能的MOGAD”，6个MS，4个OND）。在亚组分析中，LCBA- _IgGFcγ的敏感性为92.3％（CI：79.1-98.4），特异性为97.0％（CI：83.8-99.9），分别为87.2％（CI：72.6-95.7）和97.0％（CI：83.8） –99.9）用于FCBA- _IgGFcγ。

结论

LCBA-IgG ₁显示最高的特异性，但可能会错过MOG-IgG _2的反应性，其含义值得进一步研究。用LCBA-IgG _{H + L} / _IgGFcγ滴定的样品对于有意义地解释结果很重要。在亚组分析中，LCBA- _IgGFcγ的准确性最高，而FCBA- _IgGFcγ的特异性很好，但存在假阴性结果的风险。