{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:31:09Z","timestamp":1789047069078,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201488"],"award-info":[{"award-number":["82201488"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2025AFD513"],"award-info":[{"award-number":["2025AFD513"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to investigate the potential involvement of pyruvate kinase M2 (PKM2) in the pathogenesis of Guillain\u2013Barr\u00e9 syndrome (GBS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mendelian randomization (MR) analysis was used to evaluate the causal association between PKM2 expression and GBS susceptibility, with mediation analysis performed to explore immune cell\u2010mediated pathways. The association between PKM2 methylation and GBS risk was further examined using GoDMC mQTL data and GRT\u2010qPCRWAS Data Hub profiling. To validate these findings experimentally, an experimental autoimmune neuritis (EAN) mouse model was established in male C57BL\/6 mice (6\u20138 weeks) by immunization with P0180\u2013199 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&amp;E\/Luxol fast blue (LFB) staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MR analysis revealed that elevated PKM2 expression in the tibial nerve was significantly associated with an increased risk of GBS (OR: 1.75\u20136.14,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). In the EAN model, PKM2 expression in the sciatic nerve exhibited a time\u2010dependent increase (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 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\u201017a and ROR\u03b3t (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05), concomitant with a reduction in Treg cells (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 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\u2010sample MR analyses indicated that cg24327132 were positively associated with GBS risk (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 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 \u2248 0\u20130.05), visually distinct from innate immune populations (Beta \u2248 0.10\u20130.20), suggesting that perturbation of this hypomethylated state may dysregulate PKM2 expression and contribute to GBS susceptibility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PKM2 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71632","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T07:16:00Z","timestamp":1785482160000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pyruvate Kinase M2 Upregulation Is Associated With Guillain\u2013Barr\u00e9 Syndrome Risk and Immune Dysregulation: Insights From Mendelian Randomization and the Experimental Autoimmune Neuritis Model"],"prefix":"10.1002","volume":"16","author":[{"given":"Shuping","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan 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