Neuroscience Center, Department of Neurology, The First Hospital of Jilin University, Changchun, China.
Department of Neurobiology, Care Sciences & Society, Division of Neurogeriatrics, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
Clin Exp Immunol. 2023 Oct 13;213(3):363-370. doi: 10.1093/cei/uxad053.
AQP4-IgG has been considered as the pathogenic factor leading to NMOSD. However, about 20-30% of patients lack AQP4-IgG. So far, all therapeutic medicines are ineffective for NMOSD patients without AQP4 IgG. Thus AQP4-IgG is the pathogenic factor of NMOSD has been suspected and challenged. In addition, lack of efficacy of immunotherapy in NMOSD without AQP4 IgG has been a serious problem in the neurology. Identifying the clinical and laboratory characteristics and diversities between NMOSD patients with and without AQP4-IgG can be helpful to further explore the pathogenesis of NMOSD and guide clinical treatment. This is a single-centre retrospective study in The First Hospital of Jilin University, China including 92 patients diagnosed as NMOSD from January 2013 to January 2015. The characteristics of clinic, blood, cerebrospinal fluid (CSF), and image between AQP4-IgG negative (AQP4-IgG-) and AQP4-IgG positive (AQP4-IgG+) NMOSDs were compared. Our results showed that in the AQP4-IgG+ group, the ratio of women to men was 5.55, while in AQP4-IgG- group was 1.54 (P = 0.0092). In the AQP4-IgG+ patients, the expanded disability status scale (EDSS) was from 0 to 8.5, with an average of 5.550 ± 0.25, and the AQP4-IgG- patients had the EDSS score from 0 to 9, with an average of 4.032 ± 0.36 (P = 0.0006), which mainly affected movement system (P < 0.05) and superficial sensory impairment (P < 0.05). In the AQP4-IgG+ group, the blood brain barrier (BBB) permeability (P = 0.0210) and myelin basic protein (MBP) were increased (P = 0.0310) when compared to AQP4-IgG- group. Higher level IL-17 was seen in AQP4-IgG+ group than AQP4-IgG- group (P= 0.0066). Our results demonstrated that the NMOSD with AQP4-IgG more likely occurred in women and presented more severe clinical symptoms as well as significant BBB damage and increased MBP and IL-17 in CSF and blood, respectively compared with NMOSD without AQP4-IgG group. The differences in clinical and laboratory profiles between NMOSD with and without AQP4-IgG indicate the heterogeneity of NMOSD, in which AQP4-IgG may not be the only pathogenic molecule. It is necessary to find more pathogenic factors and to explore the new pathogenesis of NMOSD and therapeutic methods in the future.
AQP4-IgG 被认为是导致 NMOSD 的致病因素。然而，约 20-30%的患者缺乏 AQP4-IgG。到目前为止，所有的治疗药物对没有 AQP4 IgG 的 NMOSD 患者都没有效果。因此，AQP4-IgG 作为 NMOSD 的致病因素受到了质疑和挑战。此外，NMOSD 患者中缺乏 AQP4 IgG 的免疫治疗效果一直是神经病学中的一个严重问题。确定 NMOSD 患者中有无 AQP4-IgG 的临床和实验室特征和差异，有助于进一步探讨 NMOSD 的发病机制，并指导临床治疗。这是一项在中国吉林大学第一医院进行的单中心回顾性研究，共纳入了 92 例 2013 年 1 月至 2015 年 1 月期间诊断为 NMOSD 的患者。比较了抗水通道蛋白 4 抗体阴性（AQP4-IgG-）和抗水通道蛋白 4 抗体阳性（AQP4-IgG+）NMOSD 患者的临床、血液、脑脊液（CSF）和影像学特征。我们的结果表明，在 AQP4-IgG+组中，男女比例为 5.55，而在 AQP4-IgG-组中为 1.54（P = 0.0092）。在 AQP4-IgG+患者中，扩展残疾状况量表（EDSS）评分从 0 到 8.5，平均为 5.550±0.25，而 AQP4-IgG-患者的 EDSS 评分从 0 到 9，平均为 4.032±0.36（P = 0.0006），主要影响运动系统（P < 0.05）和浅表感觉障碍（P < 0.05）。在 AQP4-IgG+组中，血脑屏障（BBB）通透性（P = 0.0210）和髓鞘碱性蛋白（MBP）升高（P = 0.0310）。与 AQP4-IgG-组相比，AQP4-IgG+组中白细胞介素-17（IL-17）水平升高（P=0.0066）。我们的结果表明，与 AQP4-IgG 阴性 NMOSD 相比，AQP4-IgG 阳性 NMOSD 更易发生于女性，且临床症状更严重，血脑屏障损伤更明显，CSF 和血液中 MBP 和 IL-17 水平均升高。AQP4-IgG 阳性 NMOSD 和 AQP4-IgG 阴性 NMOSD 之间的临床和实验室特征差异表明 NMOSD 的异质性，其中 AQP4-IgG 可能不是唯一的致病分子。未来有必要寻找更多的致病因素，探讨 NMOSD 的新发病机制和治疗方法。
