Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre
Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre
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DOI：
10.1093/brain/awm062
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发表时间：
2007-05-01
期刊：
影响因子：
14.5
通讯作者：
Itoyama, Yasuto
中科院分区：
文献类型：
--
作者：
Takahashi, Toshiyuki;Fujihara, Kazuo;Itoyama, Yasuto
NMO-Ig G是一种针对视神经脊髓炎(NMO)的疾病特异性自身抗体，其靶抗原为水通道蛋白4(AQP4)。最近，我们利用人AQP4转基因细胞建立了一种敏感的抗AQP4抗体检测方法，该方法比原来的NMO-IgG检测方法更敏感。到目前为止，还没有关于抗AQP4抗体滴度在NMO及相关疾病中的大规模研究。我们检测了148例NMO、NMO高危综合征、多发性硬化(MS)、提示MS的临床隔离综合征和其他疾病患者的血清。分析抗AQP4抗体滴度与临床及实验室指标的关系。抗AQP4抗体检测对NMO的敏感性为91%(95%CI 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)，即其他疾病均为阴性。在21例抗AQP4抗体阳性的患者中，NMO-IgG阳性15例，NMO-IgG阴性6例。抗AQP4抗体滴度高与完全失明和MRI上广泛或大的脑部病变有关。MRI上脊髓病变长度与病情最低时抗AQP4抗体滴度呈正相关。少数患者出现短小(约.1~2个椎节段)的脊髓病变在MRI上也呈血清阳性，抗AQP4抗体滴度较低，但具有NMO的其他临床和MRI特征。大剂量甲基强的松龙治疗后，抗AQP4抗体滴度下降，随访显示，在免疫抑制的无复发期，抗AQP4抗体滴度仍然很低。当血清抗体效价大于512倍时，按I(CSF)/500(血清)的比例检测脑脊液(CSF)-抗AQP4抗体。本研究结果表明，NMO和高危综合征本质上可能是抗AQP4抗体相关性疾病，抗AQP4抗体滴度在NMO中具有重要的临床和免疫学意义。
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 I (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.