Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay
Ding Liu, Peihao Lin, Hui-Lu Li, Jie Yang, Yong You, Xiao Yang, Lihong Jiang, Caiyu Ma, Lufen Xu, Qingxia Zhang, Sha Liao, Han Chen, Jiajia Yue, Yu‐Ying Lu, Chun Lian, Yin Liu, Zhanhang Wang, Jin-Long Ye, Wei Qiu, Yaqing Shu, Haiyang Wang, Hongli Liu, Y. Lynn Wang, Chunmei Duan, Huan Yang, Xiuling Wu, Lu Zhang, Huiyu Feng, Huan Chen, Hou-Shi Zhou, Qianhui Xu, Gui‐Xian Zhao, Teng-Fei Ou, Jinliang Wang, Yuhua Lu, Zhifeng Mao, Cong Gao, Jun Guo, Hongya Zhang, Sheng Chen, Jing Li, Youming Long
Abstract
To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. Methods A retrospective observational study was conducted in 121 patients (2016–2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). Results Among cohort A (male:female=79:42; median age: 42 (14–78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00–5352.00) vs 700.00 (76.70–2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p =0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0–6) vs 0 (0–3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). Conclusions Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.