Shu Yaqing, Huang Yu, Li Qihui, Li Huilu, Li Zhibin, Ye Jinlong, Chen Jianning, Li Jianfang, Fang Ling, Li Jing, Lu Yi, Liu Libao, Luo Yongjian, Wang Zhanhang, Lu Zhengqi, Huang Zhongxi, Peng Fuhua, Qiu Wei
Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Neurology, GuangDong 999 Brain Hospital, Guangzhou, China.
Transl Psychiatry. 2025 Mar 8;15(1):78. doi: 10.1038/s41398-025-03300-y.
We presented a patient with refractory anti-GABA-R encephalitis, and constructed libraries for single-cell sequencing from the patient's peripheral blood mononuclear cells (PBMCs), cerebrospinal fluid cells, as well as four healthy volunteer's PBMCs. A distinct group of monoclonal CD8 T cells and an abnormal JAK-STAT signaling pathway was implicated in the disease. The cross-reactive protein LIM-domain-only protein 5 (LMO5) identified in the patient's thymoma, prompted the activation of the specific CD8 T cells. Furthermore, in vitro analysis revealed the involvement of the JAK-STAT pathway in LMO5-induced CD8T cell activation, a process effectively suppressed by tofacitinib, which improved the patient's clinical outcome.
我们报告了一名患有难治性抗γ-氨基丁酸受体（GABA-R）脑炎的患者，并构建了来自该患者外周血单个核细胞（PBMC）、脑脊液细胞以及四名健康志愿者PBMC的单细胞测序文库。一组独特的单克隆CD8 T细胞和异常的JAK-STAT信号通路与该疾病有关。在患者胸腺瘤中鉴定出的交叉反应蛋白仅含LIM结构域蛋白5（LMO5）促使特定CD8 T细胞活化。此外，体外分析揭示了JAK-STAT通路参与LMO5诱导的CD8 T细胞活化，托法替布可有效抑制这一过程，从而改善了患者的临床结局。
