儿童乙型脑炎后自身免疫性脑炎：一项前瞻性研究。
Autoimmune encephalitis after Japanese encephalitis in children: A prospective study.
机构信息
Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China; Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China; National Clinical Research Center for Child Health and Disorders, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Pediatrics, Chongqing, China.
Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China; National Clinical Research Center for Child Health and Disorders, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Pediatrics, Chongqing, China.
出版信息
J Neurol Sci. 2021 May 15;424:117394. doi: 10.1016/j.jns.2021.117394. Epub 2021 Mar 17.
OBJECTIVE
To explore anti-neuronal surface antibodies and identify associated serum predictors of autoimmune encephalitis after Japanese encephalitis (JE).
METHODS
This prospective study first detected anti-neuronal surface antibodies and cytokines in the serum and cerebrospinal fluid (CSF) of JE patients within one week of symptom onset. Anti-neuronal surface antibodies and cytokines in the serum were detected on day 21 post-JE. If the patients relapsed during the convalescent phase, we simultaneously detected JE virus RNA and cytokines in the CSF, as well as anti-neuronal surface antibodies in the serum and CSF.
RESULTS
All 31 patients were negative for anti-neuronal surface antibodies at the onset of JE in the serum and CSF. During the convalescent phase, five patients developed autoimmune encephalitis (two had anti-N-methyl-d-aspartate receptor [NMDAR] antibodies, one had γ-aminobutyric acid-B receptor [GABAR] antibodies, and two had other antibodies against unknown neuronal surface antigens). Patients who developed autoimmune encephalitis experienced more severe outcomes than those who did not at the one-year follow-up (p = 0.044). The levels of serum CXCL13 and IL-6, as well as CXCL13, BAFF, CXCL10, and MMP-9 in the CSF were increased in the convalescent phase compared to the acute phase in patients who developed autoimmune encephalitis (p < 0.05).
CONCLUSION
In addition to anti-NMDAR antibodies, anti-GABAR antibodies and antibodies against unknown neuronal surface antigens can trigger autoimmune encephalitis following JE. Patients who developed autoimmune encephalitis had a poorer prognosis at the one-year follow-up. Serum CXCL13 may represent a predictor of autoimmune encephalitis after JE.
目的
探讨抗神经元表面抗体，并确定日本脑炎（JE）后自身免疫性脑炎的相关血清预测因子。
方法
本前瞻性研究首先在发病后一周内检测 JE 患者血清和脑脊液（CSF）中的抗神经元表面抗体和细胞因子。在 JE 后第 21 天检测血清中的抗神经元表面抗体和细胞因子。如果患者在恢复期复发，我们同时检测 CSF 中的 JE 病毒 RNA 和细胞因子，以及血清和 CSF 中的抗神经元表面抗体。
结果
所有 31 例患者在 JE 发病时血清和 CSF 中均未检测到抗神经元表面抗体。在恢复期，有 5 例患者发生自身免疫性脑炎（2 例有抗 N-甲基-D-天冬氨酸受体[NMDA]抗体，1 例有 γ-氨基丁酸-B 受体[GABAR]抗体，2 例有针对未知神经元表面抗原的其他抗体）。在一年随访时，发生自身免疫性脑炎的患者比未发生自身免疫性脑炎的患者预后更差（p=0.044）。与急性期相比，发生自身免疫性脑炎的患者在恢复期时血清 CXCL13 和 IL-6 以及 CSF 中的 BAFF、CXCL10 和 MMP-9 水平升高（p<0.05）。
结论
除抗 NMDA 抗体外，抗 GABAR 抗体和针对未知神经元表面抗原的抗体也可引发 JE 后自身免疫性脑炎。发生自身免疫性脑炎的患者在一年随访时预后较差。血清 CXCL13 可能是 JE 后自身免疫性脑炎的预测因子。
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