Neuroimmunology Unit, Department of Pathophysiology, Faculty of Medicine, National and Kapodistrian University of Athens, Greece.
J Neuroimmunol. 2013 Jul 15;260(1-2):117-20. doi: 10.1016/j.jneuroim.2013.04.017. Epub 2013 May 11.
Autoantibodies against the water channel AQP4, expressed predominately in central nervous system astrocytes, are markers and pathogenic factors in Devic's disease. In this study we examined whether Multiple Sclerosis (MS) patients recognize antigenic epitopes on AQP4 that may define distinct disease subsets. We screened sera from 45 patients with relapsing-remitting MS (RRMS) and 13 patients with primary progressive MS (PMS). 23 Neuromyelitis Optica (NMO) patients previously characterized were used as assay positive/negative controls. Sera from 23 patients with Systemic Lupus Erythematosus, 23 with primary Sjogren syndrome without neurological involvement and from 28 healthy individuals were also used as controls. NMO-positive sera exhibited reactivity against the intracellular epitope AQPaa252-275, confirming previous observations. All RRMS sera tested negative for anti-AQP4 antibodies using a cell-based assay, but surprisingly, 13% of them reacted with the epitope AQPaa252-275. PMS, healthy and disease controls showed no specific reactivity. Whether these antibodies define distinct MS subsets and have a pathogenic potential pointing to convergent pathogenetic mechanism with NMO, or are simply markers of astrocytic damage, remains to be determined.
自身抗体针对水通道 AQP4，主要表达于中枢神经系统星形胶质细胞，是 Devic 病的标志物和致病因素。在这项研究中，我们研究了多发性硬化症（MS）患者是否识别 AQP4 上的抗原表位，这些表位可能定义不同的疾病亚型。我们筛选了 45 例复发缓解型多发性硬化症（RRMS）和 13 例原发性进展型多发性硬化症（PMS）患者的血清。以前作为阳性/阴性对照的 23 例视神经脊髓炎（NMO）患者用于该实验。还使用了 23 例系统性红斑狼疮、23 例无神经系统受累的原发性干燥综合征患者和 28 例健康个体的血清作为对照。NMO 阳性血清对细胞内表位 AQPaa252-275 表现出反应性，证实了先前的观察结果。所有 RRMS 血清均使用基于细胞的测定法检测到抗 AQP4 抗体为阴性，但令人惊讶的是，其中 13%的血清与表位 AQPaa252-275 发生反应。PMS、健康对照和疾病对照均无特异性反应。这些抗体是否定义了不同的 MS 亚型，是否具有致病性潜力，指向与 NMO 趋同的发病机制，或者仅仅是星形胶质细胞损伤的标志物，仍有待确定。
