From the Departments of Laboratory Medicine and Pathology (Y.J., J.P.F., V.A.L., A.M.L.Q., A.M., R.I., S.J.P.), Neurology (V.A.L., A.M., C.C., B.G.W., C.F.L., S.J.P.), Immunology (V.A.L.), and Health Sciences Research (S.M.J., C.Y.S.), College of Medicine, Mayo Clinic, Rochester, MN; Department of Neurology (D.M.W.), College of Medicine, Mayo Clinic, Scottsdale, AZ; and Department of Neurology (E.A.S.), College of Medicine, Mayo Clinic, Jacksonville, FL.
Neurology. 2013 Oct 1;81(14):1197-204. doi: 10.1212/WNL.0b013e3182a6cb5c. Epub 2013 Aug 30.
To 1) determine, using contemporary recombinant antigen-based assays, the aquaporin-4 (AQP4)-immunoglobulin G (IgG) detection rate in sequential sera of patients assigned a clinical diagnosis of neuromyelitis optica (NMO) but initially scored negative by tissue-based indirect immunofluorescence (IIF) assay; and 2) evaluate the impact of serostatus on phenotype and outcome.
From Mayo Clinic records (2005-2011), we identified 163 patients with NMO; 110 (67%) were seropositive by IIF and 53 (33%) were scored seronegative. Available stored sera from 49 "seronegative" patients were tested by ELISA, AQP4-transfected cell-based assay, and in-house fluorescence-activated cell sorting assay. Clinical characteristics were compared based on final serostatus.
Thirty of the 49 IIF-negative patients (61%) were reclassified as seropositive, yielding an overall AQP4-IgG seropositivity rate of 88% (i.e., 12% seronegative). The fluorescence-activated cell sorting assay improved the detection rate to 87%, cell-based assay to 84%, and ELISA to 79%. The sex ratio (female to male) was 1:1 for seronegatives and 9:1 for seropositives (p < 0.0001). Simultaneous optic neuritis and transverse myelitis as onset attack type (i.e., within 30 days of each other) occurred in 32% of seronegatives and in 3.6% of seropositives (p < 0.0001). Relapse rate, disability outcome, and other clinical characteristics did not differ significantly.
Serological tests using recombinant AQP4 antigen are significantly more sensitive than tissue-based IIF for detecting AQP4-IgG. Testing should precede immunotherapy; if negative, later-drawn specimens should be tested. AQP4-IgG-seronegative NMO is less frequent than previously reported and is clinically similar to AQP4-IgG-seropositive NMO.
1）使用现代基于重组抗原的检测方法，确定被临床诊断为视神经脊髓炎（NMO）但最初基于组织的间接免疫荧光（IIF）检测呈阴性的患者连续血清中的水通道蛋白 4（AQP4）-免疫球蛋白 G（IgG）检出率；2）评估血清状态对表型和结局的影响。
我们从梅奥诊所的记录（2005-2011 年）中确定了 163 名 NMO 患者；110 名（67%）通过 IIF 呈阳性，53 名（33%）呈阴性。对 49 名“阴性”患者的可用存储血清进行了酶联免疫吸附试验、AQP4 转染细胞检测和内部荧光激活细胞分选检测。根据最终的血清状态比较了临床特征。
49 名 IIF 阴性患者中有 30 名（61%）被重新分类为阳性，AQP4-IgG 的总阳性率为 88%（即 12%为阴性）。荧光激活细胞分选检测将检出率提高到 87%，细胞检测为 84%，酶联免疫吸附试验为 79%。阴性组的性别比（女性对男性）为 1:1，阳性组为 9:1（p<0.0001）。同时视神经炎和横贯性脊髓炎作为首发攻击类型（即相互之间在 30 天内）发生在 32%的阴性组和 3.6%的阳性组（p<0.0001）。复发率、残疾结局和其他临床特征无显著差异。
使用重组 AQP4 抗原的血清学检测明显比基于组织的 IIF 检测更敏感，用于检测 AQP4-IgG。检测应在免疫治疗之前进行；如果阴性，应检测后续样本。AQP4-IgG 阴性的 NMO 比之前报道的更为罕见，且与 AQP4-IgG 阳性的 NMO 临床相似。
