Individualized therapy guided by single-cell sequencing in anti-GABA_AR encephalitis

We presented a patient with refractory anti-GABA_A-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 CD8⁺T cell activation, a process effectively suppressed by tofacitinib, which improved the patient's clinical outcome.