285917 20260407160731.0 10.3389/fimmu.2025.1678840 doi pmid:41929475 pmid pmc:PMC13038563 pmc DZNE-2026-00363 English 610 Pietrock, Charlotte 0 Neuronal autoantibodies associated with poorer neuropsychological and motor outcomes 6 months after stroke: results from the PHYS-STROKE trial. Lausanne 2026 Frontiers Media article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1775570666_6266 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Trial registration: clinicaltrials.gov NCT01953549 Emerging evidence suggests a role of neuronal autoantibodies (nAbs) for long-term stroke outcomes. However, data remain limited and many domains unexamined. We present a comprehensive analysis of nAbs and their association with a broad range of outcome measures at multiple timepoints in the six months following moderate stroke.In this explorative analysis of the multicenter, randomized-controlled PHYS-STROKE trial, serum samples from stroke patients were tested for 40 nAbs at baseline (5-45 days post-stroke), post-intervention (4 weeks after baseline), and at three and six months after stroke. Generalized estimating equation (GEE)-models were used to evaluate the dynamics of nAbs over time. Multiple linear regression models were applied to investigate the prognostic role of nAbs on various outcomes at three and six months.Two hundred stroke patients (41% female; mean age: 69 ± 12 years, median acute National Institutes of Health Stroke Scale: 8) were enrolled. Cell-based seroreactivity decreased from baseline to six months (39 of 183 patients [21%] vs. 18 of 137 patients [13%]). while tissue-based reactivity increased (4 of 183 patients [2%] vs. 9 of 137 patients [7%]). The GEE applied to the imputed dataset indicated a statistically significant decreased likelihood of seroreactive nAbs in cell-based assays from baseline to six months (95%CI = 0.36 to 0.98; p = 0.041), while tissue-based analyses showed an inverse effect for the same time period (95%CI = 1.11 to 8.51; p = 0.032). The most frequently detected antibody was anti-N-Methyl-D-Aspartate receptor GluN1 (NMDAR (IgM, IgA, IgG), 30 patients [15.1%]). Baseline nAB seropositivity was associated with worse depression scores (95%CI = 0.03 to 7.82; p = 0.048) and poorer subjective mobility (95%CI=0.04 to 0.99; p = 0.033) at six months post-stroke. NMDAR-antibodies at baseline were linked to a lower subjective overall health rating (95%CI = -17.96 to -0.16; p = 0.046) and lower maximum walking speed (95%CI = -0.57 to -0.03; p = 0.027) at six months. No associations were found with outcomes at three months.Antibody seropositivity was associated with poorer outcomes in certain neuropsychological and motor outcome measures at six but not three months post-stroke. These findings require confirmation in larger cohorts and emphasize the need for future studies with longer follow-up periods in this patient population.clinicaltrials.gov NCT01953549. 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de NMDAR Other biomarker Other neuroimmunology Other neuronal autoantibodies Other outcome Other recovery Other stroke Other Autoantibodies NLM Chemicals Biomarkers NLM Chemicals Humans MeSH Autoantibodies: blood MeSH Autoantibodies: immunology MeSH Female MeSH Male MeSH Aged MeSH Stroke: immunology MeSH Stroke: blood MeSH Stroke: psychology MeSH Middle Aged MeSH Neurons: immunology MeSH Aged, 80 and over MeSH Prognosis MeSH Neuropsychological Tests MeSH Biomarkers: blood MeSH Neumann, Konrad 1 Rentzsch, Kristin 2 Prüss, Harald P:(DE-2719)2810931 3 dzne Meisel, Andreas 4 Endres, Matthias P:(DE-2719)2811033 5 dzne Nave, Alexander Heinrich 6 10.3389/fimmu.2025.1678840 Vol. 16, p. 1678840 PERI:(DE-600)2606827-8 1678840 Frontiers in immunology 16 2026 1664-3224 http://pub.dzne.de/record/285917/files/DZNE-2026-00363.pdf Restricted http://pub.dzne.de/record/285917/files/DZNE-2026-00363.pdf?subformat=pdfa pdfa Restricted Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2810931 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 5 P:(DE-2719)2811033 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 0 JCR StatID:(DE-HGF)0100 StatID FRONT IMMUNOL : 2022 2024-12-28 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2024-12-28 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2024-12-28 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2023-12-29T15:23:07Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2023-12-29T15:23:07Z Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Anonymous peer review 2023-12-29T15:23:07Z Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ 2023-12-29T15:23:07Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2024-12-28 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2024-12-28 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2024-12-28 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2024-12-28 IF >= 5 StatID:(DE-HGF)9905 StatID FRONT IMMUNOL : 2022 2024-12-28 Article Processing Charges StatID:(DE-HGF)0561 StatID 2024-12-28 Fees StatID:(DE-HGF)0700 StatID 2024-12-28 I:(DE-2719)1810003 AG Prüß Autoimmune Encephalopathies 0 I:(DE-2719)1811005 AG Endres Interdisciplinary Dementia Research 1 journal EDITORS VDBINPRINT I:(DE-2719)1810003 I:(DE-2719)1811005 UNRESTRICTED