Takahashi Toshiyuki, Fujihara Kazuo, Nakashima Ichiro, Misu Tatsuro, Miyazawa Isabelle, Nakamura Masashi, Watanabe Shohei, Shiga Yusei, Kanaoka Chihiro, Fujimori Juichi, Sato Shigeru, Itoyama Yasuto
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan.
Brain. 2007 May;130(Pt 5):1235-43. doi: 10.1093/brain/awm062. Epub 2007 Apr 19.
NMO-IgG is a disease-specific autoantibody for neuromyelitis optica (NMO) and its target antigen is aquaporin-4 (AQP4) water channel. Recently, we established a sensitive anti-AQP4 antibody assay using human AQP4-transfected cells, which appeared more sensitive than the original NMO-IgG assay. So far, there has been no large-scale study on anti-AQP4 antibody titre in NMO and related disorders. We tested 148 sera of patients with NMO, high-risk syndrome of NMO, multiple sclerosis (MS), clinically isolated syndrome suggestive of MS and miscellaneous diseases. We analysed the relation of anti-AQP4 antibody titres and clinical and laboratory parameters. The sensitivity of anti-AQP4 antibody assay was 91% (95% CI 79-100) for NMO and 85% (65-100) for high-risk syndrome, and the specificity was 100% (91-100) for NMO and high-risk syndrome, that is, none with the other disorders was positive. Among 21 anti-AQP4 antibody-positive cases whose NMO-IgG were tested, 15 were NMO-IgG-positive and 6 were NMO-IgG-negative. Higher anti-AQP4 antibody titres were associated with complete blindness and extensive or large cerebral lesions on MRI. The lengths of spinal cord lesions on MRI were positively correlated with the titres of anti-AQP4 antibody at the nadir of exacerbations. A few patients who had short (approx. one to two vertebral segments) spinal cord lesions on MRI were also seropositive with low anti-AQP4 antibody titres, but did have other clinical and MRI features of NMO. Anti-AQP4 antibody titres became lower after high-dose methylprednisolone, and a follow-up showed anti-AQP4 antibody titres remained low in relapse-free periods under immunosuppression. Cerebrospinal fluid (CSF)-anti-AQP4 antibody was detected when the serum-antibody titres exceeded 512x, at the ratio of 1 (CSF) to 500 (serum). Using a sensitive assay, the results of the present study suggest that NMO and high-risk syndrome may be essentially anti-AQP4 antibody-associated disorders, and that the anti-AQP4 antibody titres have significant clinical and immunological implications in NMO.
视神经脊髓炎免疫球蛋白（NMO-IgG）是视神经脊髓炎（NMO）的一种疾病特异性自身抗体，其靶抗原为水通道蛋白4（AQP4）水通道。最近，我们利用转染人AQP4的细胞建立了一种敏感的抗AQP4抗体检测方法，该方法似乎比原来的NMO-IgG检测方法更敏感。到目前为止，尚未有关于NMO及相关疾病中抗AQP4抗体滴度的大规模研究。我们检测了148例NMO患者、NMO高危综合征患者、多发性硬化（MS）患者、提示MS的临床孤立综合征患者及其他杂病患者的血清。我们分析了抗AQP4抗体滴度与临床及实验室参数之间的关系。抗AQP4抗体检测对NMO的敏感性为91%（95%可信区间79 - 100），对高危综合征的敏感性为85%（65 - 100），对NMO和高危综合征的特异性为100%（91 - 100），即其他疾病患者均为阴性。在检测了NMO-IgG的21例抗AQP4抗体阳性病例中，15例NMO-IgG阳性，6例NMO-IgG阴性。较高的抗AQP4抗体滴度与完全失明以及MRI上广泛或大面积脑损害相关。MRI上脊髓损害的长度与病情加重最低点时抗AQP4抗体滴度呈正相关。少数MRI显示脊髓损害较短（约1至2个椎体节段）的患者抗AQP4抗体滴度较低但血清学阳性，且确实具有NMO的其他临床和MRI特征。大剂量甲泼尼龙治疗后抗AQP4抗体滴度降低，随访显示在免疫抑制下无复发期抗AQP4抗体滴度仍保持较低水平。当血清抗体滴度超过512倍时可检测到脑脊液（CSF）-抗AQP4抗体，脑脊液与血清的比例为1∶500。本研究结果表明，使用敏感检测方法，NMO和高危综合征可能本质上是抗AQP4抗体相关疾病，且抗AQP4抗体滴度在NMO中具有重要的临床和免疫学意义。
