Clinical utility of testing AQP4-IgG in CSF: Guidance for physicians.
Clinical utility of testing AQP4-IgG in CSF: Guidance for physicians.
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DOI：
10.1212/nxi.0000000000000231
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Pittock SJ
中科院分区：
文献类型：
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作者：
Majed M;Fryer JP;McKeon A;Lennon VA;Pittock SJ
使用优化灵敏度和特异性的检测方法，确定水通道蛋白4免疫球蛋白G（AQP 4-IgG）检测的最具信息量的标本类型。回顾了提交给马约诊所神经免疫学实验室的101，065例个体患者标本中AQP 4-IgG的纵向服务检测结果。使用基于M1-AQP 4转染细胞的测定法（固定AQP 4-CBA Euroimmun试剂盒[市售CBA]和活体内部流式细胞术[FACS]）检测了616例患者的血清/CSF配对样本。比较了来自视神经脊髓炎（NMO）患者或高危患者的58份时间匹配的配对标本（间隔≤30天）的敏感性。2007年，CSF作为唯一初始标本提交的频率为1/50，2015年为1/5。在616份配对标本中，无一例CSF阳性和血清阴性。在58个时间匹配的配对样本中，通过FACS或商业CBA检测血清中的AQP 4-IgG比CSF中的更敏感（分别为p = 0.06和p < 0.001）。血清滴度>1：100预测CSF阳性（p < 0.001）。CSF阳性的概率在发作时间附近更大（p = 0.03）。128例神经系统患者的对照标本均未检出阳性。流式细胞术和商业CBA检测AQP 4-IgG在CSF中的灵敏度低于血清。数据表明，大多数AQP 4-IgG产生于外周淋巴组织，并且IgG以致病量穿透CNS需要临界血清/CSF梯度。血清是AQP 4-IgG检测的最佳和最具成本效益的标本。本研究提供了IV类证据，证明对于NMO或NMOSD患者，CSF检测AQP 4-IgG的灵敏度低于血清。
To define, using assays of optimized sensitivity and specificity, the most informative specimen type for aquaporin-4 immunoglobulin G (AQP4-IgG) detection. Results were reviewed from longitudinal service testing for AQP4-IgG among specimens submitted to the Mayo Clinic Neuroimmunology Laboratory from 101,065 individual patients. Paired samples of serum/CSF were tested from 616 patients, using M1-AQP4-transfected cell-based assays (both fixed AQP4-CBA Euroimmun kit [commercial CBA] and live in-house flow cytometry [FACS]). Sensitivities were compared for 58 time-matched paired specimens (drawn ≤30 days apart) from patients with neuromyelitis optica (NMO) or high-risk patients. The frequency of CSF submission as sole initial specimen was 1 in 50 in 2007 and 1 in 5 in 2015. In no case among 616 paired specimens was CSF positive and serum negative. In 58 time-matched paired specimens, AQP4-IgG was detected by FACS or by commercial CBA more sensitively in serum than in CSF (respectively, p = 0.06 and p < 0.001). A serum titer >1:100 predicted CSF positivity (p < 0.001). The probability of CSF positivity was greater around attack time (p = 0.03). No control specimen from 128 neurologic patients was positive by either assay. FACS and commercial CBA detection of AQP4-IgG is less sensitive in CSF than in serum. The data suggest that most AQP4-IgG is produced in peripheral lymphoid tissues and that a critical serum/CSF gradient is required for IgG to penetrate the CNS in pathogenic quantity. Serum is the optimal and most cost-effective specimen for AQP4-IgG testing. This study provides Class IV evidence that for patients with NMO or NMOSD, CSF is less sensitive than serum for detection of AQP4-IgG.