Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota2Department of Neurology, Mayo Clinic, Rochester, Minnesota.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota2Department of Neurology, Mayo Clinic, Rochester, Minnesota3Department of Immunology, Mayo Clinic, Rochester, Minnesota.
JAMA Neurol. 2014 Nov;71(11):1433-6. doi: 10.1001/jamaneurol.2014.1581.
Using an aquaporin-4 (AQP4) M1-isoform-specific enzyme-linked immunosorbent assay (ELISA) and a fixed transfected cell-based assay (CBA), we tested AQP4-IgG in a northern California population representative cohort of 3293 potential cases with multiple sclerosis (MS). Seropositive cases were tested additionally by fluorescence-activated cell sorting, a live transfected cell-based assay.
Sera samples were available in 1040 cases; 7 yielded positive results, 4 by ELISA alone and 3 by both ELISA and CBA. Clinical data (episodes of optic neuritis and longitudinally extensive transverse myelitis [reported on at least 1 magnetic resonance imaging spine]) supported the alternative diagnosis of neuromyelitis optica for 2 patients as seropositive by both ELISA and CBA. These 2 patients alone tested positive by a fluorescence-activated cell-sorting assay. The diagnosis of MS was considered correct in the other 5 patients. Thus, 5 ELISA results and 1 fixed CBA result were false positive.
Sensitive serological evaluation for AQP4-IgG in this large population-representative cohort of predominantly white non-Hispanic patients with MS reveals that neuromyelitis optica spectrum disorder is rarely misdiagnosed as MS in contemporary US neurological practice (0.2%). The frequency of a false-positive result for ELISA and CBA in this MS cohort were 0.5% and 0.1%, respectively. This finding reflects the superior specificity of CBA and justifies caution in interpreting AQP4-IgG results obtained by ELISA.
使用水通道蛋白 4（AQP4）M1-同工型特异性酶联免疫吸附测定（ELISA）和固定转染细胞基础测定（CBA），我们在加利福尼亚北部的一个具有代表性的 3293 例多发性硬化症（MS）潜在病例队列中测试了 AQP4-IgG。通过荧光激活细胞分选和活转染细胞基础测定对阳性血清进行了进一步检测。
1040 例病例中有血清样本可用；7 例结果阳性，4 例仅通过 ELISA 阳性，3 例通过 ELISA 和 CBA 阳性。临床数据（视神经炎和纵向广泛横贯性脊髓炎发作[至少有 1 次磁共振成像脊柱报告]）支持通过 ELISA 和 CBA 均呈阳性的 2 例患者的视神经脊髓炎谱系疾病的替代诊断。这 2 例患者单独通过荧光激活细胞分选测定呈阳性。其他 5 例患者的 MS 诊断被认为是正确的。因此，5 例 ELISA 结果和 1 例固定 CBA 结果为假阳性。
在这个以白人非西班牙裔为主的 MS 患者的大型代表性队列中，对 AQP4-IgG 进行敏感的血清学评估表明，视神经脊髓炎谱系障碍在当代美国神经学实践中很少被误诊为 MS（0.2%）。在这个 MS 队列中，ELISA 和 CBA 的假阳性率分别为 0.5%和 0.1%。这一发现反映了 CBA 的更高特异性，并证明了通过 ELISA 获得的 AQP4-IgG 结果需要谨慎解释。
