Nasello Martina, Woodhall Mark, Xue Huiru, Mgbachi Victor, Geraldes Ruth, Leite Maria Isabel, Waters Patrick, Palace Jacqueline
Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.
Department of Neurosciences, Mental Health and Sensory Organs, Centre for Experimental Neurological Therapies (CENTERS), Sapienza University of Rome, Rome, Italy.
Brain Commun. 2025 Aug 22;7(5):fcaf312. doi: 10.1093/braincomms/fcaf312. eCollection 2025.
Detection of antibodies against aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) is essential for diagnosis of AQP4-IgG+ neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease. Uncertainties persist regarding the clinical significance of serum antibody titres to predict relapses. We aimed to analyse the trend of serum AQP4-IgG and myelin oligodendrocyte glycoprotein antibody-IgG titres during relapses and periods of clinical stability. In this retrospective study we analysed serum AQP4-IgG and myelin oligodendrocyte glycoprotein antibody -IgG titres from live cell-based assays from the Oxford Autoimmune Neurology Diagnostic Laboratory for the UK specialist NMO Service between February 2010 and June 2024. We recruited seropositive AQP4-neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease patients with serum samples available within 30 days of an attack ('attack') and at least one another sample for comparison within 1 year ('pre-attack' and 'post-attack'). Up to 3 further serum samples were selected within 2, 3 or 4 years after the attack. 117 attacks in 92 AQP4-IgG+ patients (81.5% female) and 127 attacks in 111 myelin oligodendrocyte glycoprotein antibody-IgG+ patients (62.2% female) had appropriate samples. Antibody titres significantly increased from 'pre-attack' to 'attack', decreased from 'attack' to 'post-attack', and remained stable from 2 to 4 years after attacks. Long-term immunosuppressant treatments induced a further decrease in titres during remission in both cohorts. In 40% of samples in both groups there was an increase in titre at relapse. A ≥ 2-fold increase in AQP4-IgG titres had an Odds Ratio (OR) of 6.59% and 91.5% specificity of being associated with a relapse, in myelin oligodendrocyte glycoprotein antibody-IgG+ an OR of 4.87% and 88.6% specificity. 29% (26/92) AQP4-IgG+ patients became 'seronegative' during follow: most patients (64%) had low attack titres (≤100), and the time to seroreversion related the attack titre. In contrast, 41% (46/111) myelin oligodendrocyte glycoprotein antibody-IgG+ patients became 'seronegative', mostly within the first year after the attack regardless of attack titre. In conclusion, in 60% of longitudinal serum samples from patients with AQP4-IgG or myelin oligodendrocyte glycoprotein antibody-IgG there is no increase in antibody titre. When there is an increase, it is most often at relapse. A ≥ 2-fold increase in titres should be a risk particularly in case of treatment de-escalation, non-adherence to treatment or if a pseudo-relapse is suspected.
检测抗水通道蛋白4抗体（AQP4-IgG）和髓鞘少突胶质细胞糖蛋白抗体（MOG-IgG）对于诊断AQP4-IgG阳性的视神经脊髓炎谱系障碍和髓鞘少突胶质细胞糖蛋白抗体相关疾病至关重要。血清抗体滴度预测复发的临床意义仍存在不确定性。我们旨在分析复发期间和临床稳定期血清AQP4-IgG和髓鞘少突胶质细胞糖蛋白抗体-IgG滴度的变化趋势。在这项回顾性研究中，我们分析了2010年2月至2024年6月期间英国专科视神经脊髓炎服务中心牛津自身免疫性神经病诊断实验室基于活细胞检测的血清AQP4-IgG和髓鞘少突胶质细胞糖蛋白抗体-IgG滴度。我们招募了血清学阳性的AQP4视神经脊髓炎谱系障碍和髓鞘少突胶质细胞糖蛋白抗体相关疾病患者，这些患者在发作后30天内有可用血清样本（“发作期”），且在1年内至少有另一个样本用于比较（“发作前”和“发作后”）。在发作后2、3或4年内最多再选择3份血清样本。92例AQP4-IgG阳性患者（81.5%为女性）发生117次发作，111例髓鞘少突胶质细胞糖蛋白抗体-IgG阳性患者（62.2%为女性）发生127次发作，均有合适的样本。抗体滴度从“发作前”到“发作期”显著升高，从“发作期”到“发作后”降低，发作后2至4年保持稳定。长期免疫抑制治疗在两个队列的缓解期均导致滴度进一步下降。两组40%的样本在复发时滴度升高。AQP4-IgG滴度≥2倍升高时，与复发相关的比值比（OR）为6.59%，特异性为91.5%；髓鞘少突胶质细胞糖蛋白抗体-IgG阳性时，OR为4.87%，特异性为88.6%。29%（26/92）的AQP4-IgG阳性患者在随访期间变为“血清学阴性”：大多数患者（64%）发作时滴度较低（≤100），血清转阴时间与发作时滴度有关。相比之下，41%（46/111）的髓鞘少突胶质细胞糖蛋白抗体-IgG阳性患者变为“血清学阴性”，大多在发作后第一年内，与发作时滴度无关。总之，在AQP4-IgG或髓鞘少突胶质细胞糖蛋白抗体-IgG阳性患者的60%纵向血清样本中，抗体滴度没有升高。当滴度升高时，最常见于复发时。滴度≥2倍升高应视为一种风险因素，尤其是在治疗降级、不依从治疗或怀疑假性复发的情况下。
