Role of autoantibodies against Glutamate receptors and development of immunological treatment in patients with acute encephalitis and encephalopathies

1. 方法与患者我们对121例急性脑炎患者和6例急性脑病患者500份血清和脑脊液（csf）中GluRε2和GluRδ2的自身抗体进行了检测。这些样本来自日本各地的许多医生。利用四环素诱导系统，建立了表达nmda型GluRε2亚基或GluRδ2的NIH3T3稳定转化细胞系。将转化体的细胞提取物转移到硝化纤维素膜上以检测抗GluRs抗体的存在。将膜与患者血清或脑脊液反应，用二抗偶联碱性磷酸酶染色。结果将43例经脑脊液检查的急性脑炎或脑病患者临床分为局限性脑炎和全散性脑炎。前者在脑炎初期表现为精神症状或幻觉或孤立抽搐，但没有明显的意识损害。后者表现为脑炎发作后意识严重丧失。局限性脑炎患者血清和脑脊液中GluRε2自身抗体与预后无关。抗GluRε2自身抗体在急性期和恢复期呈阳性。全播散性脑炎患者血清GluRε2自身抗体与预后无相关性，脑脊液患者血清GluRε2自身抗体与预后有显著相关性。GluRε2自身抗体在恢复期和慢性期呈阳性。脑脊液中GluRε2自身抗体与慢性期精神发育迟滞和癫痫发作有显著相关性，与慢性期运动障碍无显著相关性。假设脑脊液中针对GluRε2的自身抗体可能与局限性脑炎（包括边缘脑炎）的脑炎发病有关，与全播散性脑炎的后遗症有关。

1. Methods and PatientsWe have studied autoantibodies against GluRε2 and GluRδ2 in sera and cerebrospinal fluids (CSFs) (500 samples) from 121 patients with acute encephalitis and 6 patients with acute encephalopathy. Those samples were donated from many doctors in all over Japan. Using tetracycline-induction system, we established stable NIH3T3 transformant cell lines expressing NMDA-type GluRε2 subunit or GluRδ2. Cell extracts of the transformants were transferred to the nitrocellulose membrane to detect the presence of antibodies against GluRs. The membrane was reacted with serum or CSF from patients, and was stained by second antibodies coupled to alkaline phosphatase.2. ResultsWe divided 43 patients with acute encephalitis or encephalopathy, whose CSFs were examined, into localized encephalitis and whole spread encephalitis, clinically. The former manifested psychic symptoms or illusion or solitary convulsion without apparent impairment of consciousness in the initial stage of encephalitis. The latter manifested profound loss of consciousness from the onset of encephalitis. In patients with localized encephalitis, autoantibodies against GluRε2 in sera and CSFs were not related with their prognoses. The autoantibodies against GluRε2 became positive in acute and recovery stages. In patients with whole spread encephalitis, autoantibodies against GluRε2 in sera were not related with their prognoses, but those in CSFs were significantly related with prognoses. The autoantibodies against GluRε2 became positive in recovery and chronic stages. Autoantibodies against GluRε2 in CSFs were related with significantly with mental retardation and epilepsy onset in chronic stages, but insignificantly with motor disturbance in chronic stages.3. HypothesesAutoantibodies against GluRε2 in CSFs might contribute to the onset of encephalitis in localized encephalitis including limbic encephalitis, and to the sequelae in whole spread encephalitis.