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@ARTICLE{Pietrock:285917,
author = {Pietrock, Charlotte and Neumann, Konrad and Rentzsch,
Kristin and Prüss, Harald and Meisel, Andreas and Endres,
Matthias and Nave, Alexander Heinrich},
title = {{N}euronal autoantibodies associated with poorer
neuropsychological and motor outcomes 6 months after stroke:
results from the {PHYS}-{STROKE} trial.},
journal = {Frontiers in immunology},
volume = {16},
issn = {1664-3224},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DZNE-2026-00363},
pages = {1678840},
year = {2026},
note = {Trial registration: clinicaltrials.gov NCT01953549},
abstract = {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.},
keywords = {Humans / Autoantibodies: blood / Autoantibodies: immunology
/ Female / Male / Aged / Stroke: immunology / Stroke: blood
/ Stroke: psychology / Middle Aged / Neurons: immunology /
Aged, 80 and over / Prognosis / Neuropsychological Tests /
Biomarkers: blood / NMDAR (Other) / biomarker (Other) /
neuroimmunology (Other) / neuronal autoantibodies (Other) /
outcome (Other) / recovery (Other) / stroke (Other) /
Autoantibodies (NLM Chemicals) / Biomarkers (NLM Chemicals)},
cin = {AG Prüß / AG Endres},
ddc = {610},
cid = {I:(DE-2719)1810003 / I:(DE-2719)1811005},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41929475},
pmc = {pmc:PMC13038563},
doi = {10.3389/fimmu.2025.1678840},
url = {https://pub.dzne.de/record/285917},
}