Aquaporin-4 Antibodies (NMO-IgG) as a Serological Marker of Neuromyelitis Optica: A Critical Review of the Literature
Aquaporin-4 Antibodies (NMO-IgG) as a Serological Marker of Neuromyelitis Optica: A Critical Review of the Literature
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DOI：
10.1111/bpa.12084
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发表时间：
2013-11-01
期刊：
影响因子：
6.4
通讯作者：
Wildemann, Brigitte
中科院分区：
文献类型：
--
作者：
Jarius, Sven;Wildemann, Brigitte
对Aquaporin-4的抗体（称为NMO-IGG或AQP4-AB）构成了神经霉素炎（NMO）的敏感且高度特异性的血清标记物，可促进NMO和经典多发性硬化症的鉴别诊断。 NMO-IGG/AQP4-AB血清阳性状态在纵向广泛的脊髓炎（LETM）或视神经炎（ON）的患者中也具有重要的预后和治疗意义。在本文中，我们对NMO-IGG/AQP4-AB测试的现有文献进行了全面审查和批判性评估。讨论了所有可用的免疫测定基于组织（IHC），基于细胞的（ICC，FACS）和基于蛋白质的（RIPA，FIPA，ELISA，Western blotting）测定的测定和它们的差异优势和缺点。对于所有已发表的研究和准确性的各种免疫测定技术的相比，计算了灵敏度，特异性以及阳性和负有可能性比率的估计值。为NMO，LETM和ON提供了子组分析，用于复发与单相疾病以及各种对照组（例如，MS与其他对照组）。 NMO-IGG/AQP4-AB测试与临床医生有关的许多方面）以及技术方面（例如，AQP4-M1与基于AQP4-M23的测定法讨论了完整的AQP4与肽底物，存储条件的影响以及冻结/解冻周期的影响）和陷阱。最后，给出了NMO-IGG/AQP4-AB血清学的临床应用的建议。
Antibodies to aquaporin-4 (called NMO-IgG or AQP4-Ab) constitute a sensitive and highly specific serum marker of neuromyelitis optica (NMO) that can facilitate the differential diagnosis of NMO and classic multiple sclerosis. NMO-IgG/AQP4-Ab seropositive status has also important prognostic and therapeutic implications in patients with isolated longitudinally extensive myelitis (LETM) or optic neuritis (ON). In this article, we comprehensively review and critically appraise the existing literature on NMO-IgG/AQP4-Ab testing. All available immunoassaysincluding tissue-based (IHC), cell-based (ICC, FACS) and protein-based (RIPA, FIPA, ELISA, Western blotting) assaysand their differential advantages and disadvantages are discussed. Estimates for sensitivity, specificity, and positive and negative likelihood ratios are calculated for all published studies and accuracies of the various immunoassay techniques compared. Subgroup analyses are provided for NMO, LETM and ON, for relapsing vs. monophasic disease, and for various control groups (eg, MS vs. other controls). Numerous aspects of NMO-IgG/AQP4-Ab testing relevant for clinicians (eg, impact of antibody titers and longitudinal testing, indications for repeat testing, relevance of CSF testing and subclass analysis, NMO-IgG/AQP4-Ab in patients with rheumatic diseases) as well as technical aspects (eg, AQP4-M1 vs. AQP4-M23-based assays, intact AQP4 vs. peptide substrates, effect of storage conditions and freeze/thaw cycles) and pitfalls are discussed. Finally, recommendations for the clinical application of NMO-IgG/AQP4-Ab serology are given.