Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
J Neuroinflammation. 2010 Sep 8;7:52. doi: 10.1186/1742-2094-7-52.
In 70-80% of cases, neuromyelitis optica (NMO) is associated with highly specific serum auto-antibodies to aquaporin-4 (termed AQP4-Ab or NMO-IgG). Recent evidence strongly suggests that AQP4-Ab are directly involved in the immunopathogenesis of NMO.
To assess the frequency, syndrome specificity, diagnostic relevance, and origin of cerebrospinal fluid (CSF) AQP4-Ab in patients with NMO spectrum disorders (NMOSD).
87 CSF samples from 37 patients with NMOSD and 42 controls with other neurological diseases were tested for AQP4-Ab in a cell based assay using recombinant human AQP4. Twenty-three paired CSF and serum samples from AQP4-Ab seropositive NMOSD patients were further analysed for intrathecal IgG synthesis to AQP4.
AQP4-Ab were detectable in 68% of CSF samples from AQP4-Ab seropositive patients with NMOSD, but in none of the CSF samples from AQP4-Ab seronegative patients with NMOSD and in none of the control samples. Acute disease relapse within 30 days prior to lumbar puncture, AQP4-Ab serum titres >1:250, and blood-CSF barrier dysfunction, but not treatment status, predicted CSF AQP4-Ab positivity. A positive AQP4-specific antibody index was present in 1/23 samples analysed.
AQP4-Ab are detectable in the CSF of most patients with NMOSD, mainly during relapse, and are highly specific for this condition. In the cohort analysed in this study, testing for CSF AQP4-Ab did not improve the sensitivity and specificity of the current diagnostic criteria for NMO. The substantial lack of intrathecal AQP4-Ab synthesis in patients with NMOSD may reflect the unique localisation of the target antigen at the blood brain barrier, and is important for our understanding of the immunopathogenesis of the disease.
在 70-80%的情况下，视神经脊髓炎（NMO）与针对水通道蛋白-4（称为 AQP4-Ab 或 NMO-IgG）的高度特异性血清自身抗体有关。最近的证据强烈表明，AQP4-Ab 直接参与了 NMO 的免疫发病机制。
评估 NMO 谱障碍（NMOSD）患者脑脊液（CSF）中 AQP4-Ab 的频率、综合征特异性、诊断相关性和起源。
使用基于细胞的测定法，使用重组人 AQP4 对 37 名 NMOSD 患者的 87 份 CSF 样本和 42 名其他神经疾病对照者的 CSF 样本进行 AQP4-Ab 检测。进一步分析 23 对 AQP4-Ab 阳性 NMOSD 患者的 CSF 和血清样本，以检测 AQP4 鞘内 IgG 合成。
AQP4-Ab 在 68%的 AQP4-Ab 阳性 NMOSD 患者的 CSF 样本中可检测到，但在 AQP4-Ab 阴性 NMOSD 患者的 CSF 样本中和对照样本中均未检测到。腰椎穿刺前 30 天内的急性疾病复发、AQP4-Ab 血清滴度>1:250 和血脑屏障功能障碍，但不是治疗状态，预测 CSF AQP4-Ab 阳性。分析的 23 个样本中有 1 个存在阳性 AQP4 特异性抗体指数。
AQP4-Ab 可在大多数 NMOSD 患者的 CSF 中检测到，主要在疾病复发期间，并且对该疾病具有高度特异性。在本研究中分析的队列中，CSF AQP4-Ab 检测并未提高 NMO 的当前诊断标准的敏感性和特异性。NMOSD 患者鞘内 AQP4-Ab 合成的大量缺乏可能反映了靶抗原在血脑屏障的独特定位，这对于我们理解疾病的免疫发病机制很重要。
