Clinical Usefulness of Cell-based Indirect Immunofluorescence Assay for the Detection of Aquaporin-4 Antibodies in Neuromyelitis Optica Spectrum Disorder

Clinical Usefulness of Cell-based Indirect Immunofluorescence Assay for the Detection of Aquaporin-4 Antibodies in Neuromyelitis Optica Spectrum Disorder
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DOI:
10.3343/alm.2012.32.5.331
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发表时间:
2012-09-01
影响因子:
4.9
通讯作者:
Kim, Byoung Joon
Kim, Byoung Joon
中科院分区:
医学3区
文献类型:
--
作者:
Kang, Eun-suk;Min, Ju-Hong;Kim, Byoung Joon

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背景:水通道蛋白-4(AQP4)抗体的存在已被认为是视神经脊髓炎谱系障碍(NMOSD)的关键特征,NMOSD是一种自身免疫性炎性脱髓鞘中枢神经系统(CNS)疾病。应用重组AQP4多肽基因转染技术制备抗原,建立细胞间接免疫荧光法(CIIFA)检测AQP4抗体,并评价其在临床诊断NMOSD中的价值。方法:以36例NMOSD患者的46份血清标本为对照,以神经科门诊入选的101例患者为对照。免疫荧光分析和荧光免疫沉淀分析(FIPA)。结果:对照组视神经脊髓炎(NMO)患者CIIFA和FIPA敏感性分别为86%和79%,高危NMO患者分别为55%和36%。CIFA测定的半定量滴度与FIPA的任意单位(荧光单位[FU])有很好的相关性(r=0.66)。CIFA和FIPA测定的滴度在NMO患者中高于高危NMO患者(分别为1:240比1:180和8,390比4,059 FU)。连续入选的101例NMO患者中,CIIFA检测AQP4抗体的频率在NMO组为100%,高危NMO组为23%,而对照组(包括多发性硬化)仅为4.6%。结论:CIIFA检测AQP4抗体为NMO和高危NMO患者提供了敏感和高度特异的诊断信息,可用于与其他脱髓鞘中枢神经系统疾病的鉴别。
Background: The presence of antibodies to aquaporin-4 (AQP4) has been identified as a key characteristic of neuromyelitis optica spectrum disorder (NMOSD), an autoimmune inflammatory demyelinating central nervous system (CNS) disorder. We evaluated the performance of a cell-based indirect immunofluorescence assay (CIIFA) for detecting AQP4 antibodies using antigen prepared with a recombinant AQP4 peptide transfection technique and assessed the usefulness of CIIFA for diagnosis of NMOSD in routine clinical practice.Methods: Forty-six serum samples from 36 patients as a comparison set and another 101 patients enrolled consecutively from a neurology clinic were included. CIIFA and fluorescence immunoprecipitation assays (FIPA) were performed. CIIFA was performed at 2 different institutions for comparison purposes.Results: CIIFA and FIPA sensitivity in the comparison set was 86% and 79% in neuromyelitis optica (NMO) patients and 55% and 36% in high-risk NMO patients, respectively. The semiquantitative titer measured by CIIFA correlated well with the arbitrary unit (fluorescence units [FU]) derived from FIPA (r = 0.66). Titers measured by CIIFA and FIPA were elevated in NMO patients compared to high-risk NMO patients (1:240 vs. 1:180 and 8,390 vs. 4,059 FU, respectively). The frequency of AQP4 antibody detection by CIIFA in 101 consecutively enrolled patients was 100% in NMO and 23% in high-risk NMO patients, while only 4.6% in control patients, including those with multiple sclerosis.Conclusions: Detection of AQP4 antibodies by CIIFA provides sensitive and highly specific diagnostic information for NMO and high-risk NMO patients, which can be used to differentiate these conditions from other demyelinating CNS diseases.