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

We presented a patient with refractory anti-GABA<sub>A</sub>-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<sup>+</sup> 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<sup>+</sup> T cells. Furthermore, in vitro analysis revealed the involvement of the JAK-STAT pathway in LMO5-induced CD8<sup>+</sup>T cell activation, a process effectively suppressed by tofacitinib, which improved the patient's clinical outcome.

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Publication Details

Journal
Translational Psychiatry
Published
2025-03-08
DOI
https://doi.org/10.1038/s41398-025-03300-y
Citations
1
Primary Topic
Autoimmune Neurological Disorders and Treatments
Type
article
Field-Weighted Citation Impact
1.39

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

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

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article en
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Abstract

We presented a patient with refractory anti-GABA<sub>A</sub>-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<sup>+</sup> 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<sup>+</sup> T cells. Furthermore, in vitro analysis revealed the involvement of the JAK-STAT pathway in LMO5-induced CD8<sup>+</sup>T cell activation, a process effectively suppressed by tofacitinib, which improved the patient's clinical outcome.

Translational PsychiatryVol. 15(1)
Jiangxi University of Traditional Chinese Medicine (CN), Sun Yat-sen University (CN), Third Affiliated Hospital of Sun Yat-sen University (CN), Guangdong 999 Brain Hospital (CN), Eighth Affiliated Hospital of Sun Yat-sen University, Southern Medical University (CN)
National Natural Science Foundation of China, Guangzhou Science and Technology Program key projects, Guangzhou Municipal Science and Technology Project
Zero hunger
Openalex Percentile: Top 23%
Autoimmune Neurological Disorders and Treatments
1.39
DOIOpen Access PDFOpenAlex
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