Diagnostic signatures and immune cell infiltration characteristics in anti-GABAR encephalitis.

Shan Qiao, Tao Xin, Wen-Yu Zhang, Yun-Fang Xie, Hai-Yun Li, Cai-San Cui, Shu-Xin Tao, Qi-Ji Liu

Journal: Journal of neuroimmunology 2024;388():578296

PMID: 38309225

Full Text on Elsevier Science View on PubMed

Abstract

PURPOSE

Anti-gamma-aminobutyric acid B receptor (GABAR) encephalitis is an uncommon form of autoimmune encephalitis associated with a poor prognosis and a high fatality rate. We aim to find diagnostic markers for anti- GABAR encephalitis as well as the effects of immune cell infiltration on this pathology.

METHODS

For quantitative proteomic analysis, isobaric tags for relative and absolute quantitation were used in conjunction with LC-MS/MS analysis. To conduct functional correlation analyses, differentially expressed proteins (DEPs) were identified. Following that, we used bioinformatics analysis to screen for and determine the diagnostic signatures of anti- GABAR encephalitis. ROC curves were used to evaluate the diagnostic values. To assess the inflammatory status of anti- GABAR encephalitis, we used cell-type identification by estimating relative subsets of the RNA transcript (CIBERSORT) and explored the link between diagnostic markers and infiltrating immune cells.

RESULTS

Overall, 108 robust DEPs (47 upregulated and 61 downregulated) were identified, of which 11 were immune related. The most impressively enriched pathways were complemented and coagulation cascades, actin cytoskeleton regulation, and cholesterol metabolism; GSEA revealed that the enriched pathways were considerably differentially connected to immune modulation. Eleven immune-related DEPs were chosen for further investigation. We developed a novel diagnostic model based on CSF1R and AZGP1 serum levels using ROC analysis (area under the ROC curve = 1). M1 macrophages and activated natural killer cells are likely to play a role in course of anti- GABAR encephalitis.

CONCLUSION

We identified CSF1R and AZGP1 are possible anti-GABAR encephalitis diagnostic indicators, and immune cell infiltration may have a significant impact on the development and occurrence of anti- GABAR encephalitis.

Address: Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China; Key Laboratory for Experimental Teratology, Ministry of Education and Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.; Department of Clinical Research, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, China.; Key Laboratory for Experimental Teratology, Ministry of Education and Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.; Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China.; Department of Neurology, Qilu Hospital of Shandong University, Jinan, China.; Department of Neurology, Liaocheng People's Hospital, Liaocheng, Shandong, China.; Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China; Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. Electronic address: [email protected].; Key Laboratory for Experimental Teratology, Ministry of Education and Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address: [email protected].

DOI: 10.1016/j.jneuroim.2024.578296

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MeSH Terms: Humans, gamma-Aminobutyric Acid, Autoantibodies, Chromatography, Liquid, Proteomics, Receptors, GABA-B, Tandem Mass Spectrometry, Encephalitis