摘要： 目的 观察视神经脊髓炎患者水通道蛋白4（AQP4）抗体在血清和脑脊液的分布特征，探讨血清AQP4 抗体与脑脊液寡克隆区带之间的关系。方法 采用酶联免疫吸附试验和间接免疫荧光法检测视神经脊髓炎和多发性硬化患者血清和脑脊液AQP4 抗体，动态定时散射比浊法检测白蛋白和IgG，等电聚焦电泳联合免疫固定法检测脑脊液寡克隆区带，免疫印迹法检测寡克隆区带阳性视神经脊髓炎患者脑脊液电泳条带中AQP4 抗体。结果 视神经脊髓炎组患者血清AQP4 抗体滴度［8.94（5.41，11.93）ng/ml］与多发性硬化组［7.34（4.76，12.00）ng/ml］相近（Z = -0.510，P = 0.610），脑脊液AQP4抗体滴度［0.45（0.42，0.47）ng/ml］高于多发性硬化组［0.41（0.40，0.41）ng/ml；Z = -2.359，P = 0.018］，而且血清水平高于脑脊液（Z = -3.702，P = 0.000）。视神经脊髓炎组患者脑脊液AQP4 抗体阳性检出率高于多发性硬化组（5/7 对1/5），但差异未达到统计学意义（Fisher 确切概率法：P = 0.242）；复发期血清AQP4 抗体滴度［8.54（5.32，11.42）ng/ml］与缓解期［9.97（5.41，13.28）ng/ml］相近（Z = -0.347，P = 0.728）；寡克隆区带阳性检出率低于多发性硬化组（3/13 对10/14）且差异有统计学意义（Fisher 确切概率法：P = 0.021）。未在寡克隆区带阳性视神经脊髓炎患者的IgG 电泳条带中检出AQP4 抗体。结论 视神经脊髓炎患者血清AQP4 抗体滴度高于脑脊液，行脑脊液AQP4 抗体检测具有一定临床意义。视神经脊髓炎患者鞘内合成IgG 能力低于多发性硬化患者，且无针对AQP4抗原的成分。

关键词: 视神经脊髓炎, 多发性硬化, 水通道蛋白质4, 寡克隆区带

Abstract: Objective  To explore the distribution characteristics of aquaporin 4 (AQP4) antibody in serum and cerebrospinal fluid (CSF) of neuromyelitis optica (NMO) patients, and to analyze the relationship between AQP4 antibody and oligoclonal bands (OB) in CSF of NMO patients.  Methods  Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA) were used to detect AQP4 antibody in serum and CSF of NMO and multiple sclerosis (MS) patients. Dynamic timed nephelometry was used to determine the levels of albumin and immunoglobulin G (IgG) in the CSF and serum. Isoelectric focusing (IEF) combined with immunofixation were used to detect OB in CSF. Western blotting was used to test whether AQP4 antibody existed in positive OB of NMO patients.  Results  The mean concentration of AQP4 antibody in serum of NMO patients [8.94 (5.41, 11.93) ng/ml] was not significantly different from that of MS patients [7.34 (4.76, 12.00) ng/ml; Z = -0.510, P = 0.610); AQP4 antibody concentration in CSF of NMO patients [0.45 (0.42, 0.47) ng/ml] was higher than that of MS patients [0.41 (0.40, 0.41) ng/ml; Z = -2.359, P = 0.018]; AQP4 antibody concentration in serum of NMO patients was higher than that in CSF (Z = -3.702, P = 0.000). The positive rate of AQP4 antibody of NMO patients was higher than that of MS patients (5/7 vs 1/5), but there was no significant difference between the two (Fisher's exact test: P = 0.242). The concentration of AQP4 antibody in relapse phase [8.54 (5.32, 11.42) ng/ml] of NMO patients was not significantly different from that in remission phase [9.97 (5.41, 13.28) ng/ml; Z = -0.347, P = 0.728]. The positive rate of OB in NMO patients was significantly lower than that in MS patients (3/13 vs 10/14; Fisher's exact test: P = 0.021). No AQP4 antibody was detected in the IgG bands of OB positive NMO patients.  Conclusions  AQP4 antibody concentration in serum of NMO patients was higher than that in CSF of NMO patients. It is of clinical significance to examine AQP4 antibody in CSF of NMO patients. Intrathecal IgG synthesis in NMO patients was lower than that in MS patients, and no AQP4 antibody was detected in the IgG bands of NMO patients with positive OB.

Key words: Neuromyelitis optica, Multiple sclerosis, Aquaporin 4, Oligoclonal bands