Evidence mapPaperPMID 42533640Full record

ArticleBrain and behavior2026

Pyruvate Kinase M2 Upregulation Is Associated With Guillain-Barré Syndrome Risk and Immune Dysregulation: Insights From Mendelian Randomization and the Experimental Autoimmune Neuritis Model.

Shuping Liu, Huiying Lu, Yuge Kang, Zheman Xiao, Qian Min, Yi Dong

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Article in Brain and behavior, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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Authors and funding

6 authors.

Shuping LiuDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
Huiying LuDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
Yuge KangDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
Zheman XiaoDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
Qian MinCancer center, Renmin Hospital of Wuhan University, Wuhan, China.
Yi DongCancer center, Renmin Hospital of Wuhan University, Wuhan, China.

Funding

National Natural Science Foundation of China 82201488Natural Science Foundation of Hubei Province 2025AFD513
6 · The paper itself

Abstract

objectiveThis study aimed to investigate the potential involvement of pyruvate kinase M2 (PKM2) in the pathogenesis of Guillain-Barré syndrome (GBS).

methodsMendelian randomization (MR) analysis was used to evaluate the causal association between PKM2 expression and GBS susceptibility, with mediation analysis performed to explore immune cell-mediated pathways. The association between PKM2 methylation and GBS risk was further examined using GoDMC mQTL data and GRT-qPCRWAS Data Hub profiling. To validate these findings experimentally, an experimental autoimmune neuritis (EAN) mouse model was established in male C57BL/6 mice (6-8 weeks) by immunization with P0180-199 peptide, with tissues collected at disease initiation (Day 8) and peak stage (Day 16). PKM2 expression dynamics, Th17/Treg (regulatory T cells) balance, and histopathological changes were assessed using, Western blot, immunohistochemistry, immunofluorescence, flow cytometry, and H&E/Luxol fast blue (LFB) staining.

resultsMR analysis revealed that elevated PKM2 expression in the tibial nerve was significantly associated with an increased risk of GBS (OR: 1.75-6.14, p < 0.05). In the EAN model, PKM2 expression in the sciatic nerve exhibited a time-dependent increase (p < 0.01), primarily localized to inflammatory infiltrates. Mechanistic studies demonstrated that PKM2 upregulation in CD4+ T cells was associated with promoted Th17 differentiation, as evidenced by the upregulation of IL-17a and RORγt (p < 0.05), concomitant with a reduction in Treg cells (p < 0.01). To further elucidate the upstream epigenetic regulation, the association between PKM2 methylation and GBS risk was investigated using GoDMC mQTL data. Among the four selected methylation sites, two-sample MR analyses indicated that cg24327132 were positively associated with GBS risk (p < 0.05). Furthermore, analysis of the GWAS Data Hub revealed that cg24327132 appeared to be preferentially hypomethylated in adaptive immune cells including regulatory T cells, CD4+ T cells, and B cells (Beta ≈ 0-0.05), visually distinct from innate immune populations (Beta ≈ 0.10-0.20), suggesting that perturbation of this hypomethylated state may dysregulate PKM2 expression and contribute to GBS susceptibility.

conclusionPKM2 upregulation is associated with GBS risk and immune dysfunction. PKM2 methylation may represent a key regulatory mechanism underlying this association. PKM2 may represent a mechanism target warranting further therapeutic investigation.

Indexed as

Guillain-Barre SyndromeNeuritis, Autoimmune, ExperimentalPyruvate KinaseAnimalsDisease Models, AnimalMaleMiceMice, Inbred C57BLTh17 CellsT-Lymphocytes, RegulatoryUp-RegulationPkm protein, mousePyruvate Kinaseexperimental autoimmune neuritismethylationPKM2Th17 cells

Identifiers

PMID42533640
PMCPMC13425601

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