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COVID-19-associated GBS (COVID-GBS) is a rare but severe post-infectious condition, and its immune mechanisms remain unclear. We profiled immune mediators in cerebrospinal fluid (CSF) and serum from COVID-GBS patients, comparing them to non-COVID GBS (Control-GBS), COVID-19 patients without neurological complications (COVID-no-GBS) and non-inflammatory neuropathy controls (Neuropathy-no-GBS). To gain mechanistic insights, we integrated publicly available single-nucleus transcriptomic data from sural nerve biopsies of neuropathy patients. IL-8 was confirmed as a key cytokine in GBS. Analysis of publicly available single-nucleus transcriptomic data from non-GBS sural nerve biopsies suggested myeloid cells as potential sources of IL-8, with evidence of autocrine signaling capacity. LIF and CD8A emerged as novel biomarkers, with this transcriptomic analysis indicating that LIF receptor components are expressed on endothelial and stromal cells, suggesting these as potential cellular targets. COVID-GBS patients exhibited unique CSF alterations and distinct serum profiles marked by altered NK cell activity, cytotoxic T-cell responses, and myeloid differentiation. Moreover, associations between inflammatory, extracellular matrix, and regulatory markers with clinical disability differed between COVID-GBS and Control-GBS, pointing to divergent immune mechanisms. Our findings suggest that GBS involves myeloid-driven cytokine responses and local LIF signaling. Analysis of publicly available transcriptomic data from non-GBS sural nerve biopsies suggests potential cellular sources and targets, though validation in GBS-affected tissue is needed. COVID-GBS features a distinct immune signature involving localized and systemic inflammation. These insights deepen our understanding of GBS pathogenesis and nominate candidate biomarkers for further validation and potential therapeutic targeting.<\/jats:p>","DOI":"10.1007\/s00109-026-02698-2","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T01:10:16Z","timestamp":1783127416000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic analysis reveals divergent inflammatory mechanisms of COVID-associated Guillain-Barr\u00e9 syndrome"],"prefix":"10.1007","volume":"104","author":[{"given":"Can","family":"Ulutekin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Can","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"S\u00faken\u00edkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Querol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Juntas-Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnau","family":"Llaurad\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anelia","family":"Dietmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Latorre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Becher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Ingelfinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Schreiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,4]]},"reference":[{"issue":"4","key":"2698_CR1","doi-asserted-by":"publisher","first-page":"2222","DOI":"10.1007\/s13311-021-01117-3","volume":"18","author":"L Querol","year":"2021","unstructured":"Querol L, Lleix\u00e0 C (2021) Novel Immunological and Therapeutic Insights in Guillain-Barr\u00e9 Syndrome and CIDP. 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