Journal Article

DZNE-2026-00449

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png CD177 Expression on Neutrophils Predicts Ischemic Stroke Outcome in Humans.

Gronewold, J. ; Hagemann, N. ; Zhang, Y. ; Jung, M. ; Fleischer, M. ; Mohamud Yusuf, A. ; Li, A. ; Wang, C. ; Dzyubenko, E. ; Scholtysik, R. ; Klein-Hitpass, L. ; Kraus, A. ; Tuz, A. A. ; Singh, V. ; Frank, B. ; Mönig, A. ; Giese, A. ; Graser, C. ; Niklas, E. M. ; da Silva Rafael, M. ; Nanthagopal, M. ; Neumann, J. ; Kufner, A. ; Liman, T. G.DZNE* ; Liu, Y. ; Minnerup, J. ; Klotz, L. ; Giebel, B. ; Tertel, T. ; Endres, M.DZNE* ; Hermann, D. M. ; Gunzer, M.

2026
Association New York, NY

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Please use a persistent id in citations: doi:10.1161/STROKEAHA.125.054673

Abstract: Neutrophil granulocytes actively contribute to tissue damage after ischemic stroke. The membrane protein CD (cluster of differentiation)177 is detectable on variable neutrophil numbers in most individuals (CD177 wild-type [CD177WT] genotype), whereas ≈5% of the general population completely lack CD177 (CD177-deficient [CD177null] genotype). Despite its known relevance in vasculitis, the role of ischemic stroke remains unknown.In 2 prospective cohorts of patients with first-ever ischemic stroke (PROSCIS-B [Prospective Cohort With Incident Stroke Berlin], NOFF-S [Neutrophils: Origin, Fate & Function Stroke]), we assessed the effect of CD177null and CD177WT status on stroke severity and outcome (National Institutes of Health Stroke Scale and modified Rankin Scale) over 1 year or 3 months poststroke, respectively. By flow cytometry, we stratified CD177 expression level as CD177neg, CD177dim, and CD177high. The predictive value of the CD177 state was evaluated by multivariable regression and discrimination analyses.In PROSCIS-B (n=579; mean age, 68.1 years; 38.5% women) and NOFF-S (n=236, 68.4 years, 36.9% women), similar rates of patients were CD177null (n=26 [4.5%] and n=10 [4.2%], respectively). Patients with CD177null had a higher probability of unfavorable stroke outcome (modified Rankin Scale score 3-6) than patients with CD177WT (n=8 of 21 [38.1%] versus 90 of 462 [19.5%] with follow-up, P=0.05, in PROSCIS-B; n=8 of 10 [80.0%] versus n=23 of 142 [16.2%] with follow-up, P<0.0001, in NOFF-S). This association remained when adjusted for age, sex, initial stroke severity defined by National Institutes of Health Stroke Scale score, stroke subtype defined by TOAST (Trial of ORG 10172 in Acute Stroke Treatment), and reperfusion treatment (relative risk, 3.8 [95% CI, 2.0-7.1]; P<0.001, in NOFF-S). In NOFF-S, the proportion of CD177dim neutrophils at admission was negatively associated with stroke severity at admission, while that of CD177high neutrophils predicted a favorable clinical outcome after 3 months. CD177 expression level significantly improved the prediction of stroke outcome in addition to clinical adjustment variables in area under the curve, net reclassification improvement, and integrated discrimination improvement analyses (P=0.004, P=0.001, and P<0.001, respectively, for CD177high).CD177 expression at admission is an easy-to-measure biomarker for patient stratification. CD177 holds potential as a therapeutic target to modulate immune responses after stroke.URL: https://www.clinicaltrials.gov; Unique identifier: NCT01363856. URL: https://drks.de/search/en/trial/Unique identifier: DRKS00030825.

Keyword(s): Humans (MeSH) ; Male (MeSH) ; Female (MeSH) ; GPI-Linked Proteins: genetics (MeSH) ; Aged (MeSH) ; Neutrophils: metabolism (MeSH) ; Ischemic Stroke: genetics (MeSH) ; Ischemic Stroke: blood (MeSH) ; Ischemic Stroke: diagnosis (MeSH) ; Ischemic Stroke: metabolism (MeSH) ; Middle Aged (MeSH) ; Prospective Studies (MeSH) ; Isoantigens: genetics (MeSH) ; Isoantigens: biosynthesis (MeSH) ; Isoantigens: blood (MeSH) ; Aged, 80 and over (MeSH) ; Brain Ischemia (MeSH) ; Prognosis (MeSH) ; Cohort Studies (MeSH) ; Predictive Value of Tests (MeSH) ; Receptors, Cell Surface (MeSH) ; flow cytometry ; innate immunity ; ischemic stroke ; neutrophils ; stroke ; stroke rehabilitation ; value of tests ; GPI-Linked Proteins ; CD177 protein, human ; Isoantigens ; Receptors, Cell Surface

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Contributing Institute(s):

1. Interdisciplinary Dementia Research (AG Endres)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; Allianz-Lizenz ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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