Systemic S100A8/A9 in patients with moderate to severe acute ischemic stroke: Exploratory analysis of inflammation and functional outcome
Introduction: S100A8/A9, a danger-associated molecular pattern (DAMP), is released from leukocytes, mainly neutrophils, and augments inflammation and tissue damage. The role of systemic plasma levels of S100A8/A9 in stroke-related inflammation and its association with clinical outcome lacks sufficie...
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Elsevier
2025-08-01
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| Series: | Brain, Behavior, & Immunity - Health |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666354625000997 |
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| author | Christoph Vollmuth Felipe A. Montellano Cornelia Fiessler Fabian Essig Christian Hametner Alexander M. Kollikowski Vivian Vogt Mirko Pham Peter U. Heuschmann Karl Georg Haeusler Guido Stoll Hermann Neugebauer Michael K. Schuhmann |
| author_facet | Christoph Vollmuth Felipe A. Montellano Cornelia Fiessler Fabian Essig Christian Hametner Alexander M. Kollikowski Vivian Vogt Mirko Pham Peter U. Heuschmann Karl Georg Haeusler Guido Stoll Hermann Neugebauer Michael K. Schuhmann |
| author_sort | Christoph Vollmuth |
| collection | DOAJ |
| description | Introduction: S100A8/A9, a danger-associated molecular pattern (DAMP), is released from leukocytes, mainly neutrophils, and augments inflammation and tissue damage. The role of systemic plasma levels of S100A8/A9 in stroke-related inflammation and its association with clinical outcome lacks sufficient data. Methods: Prospective, monocentric, observational study including patients with moderate to severe acute ischemic anterior circulation stroke [National Institutes of Health Stroke Scale (NIHSS) score ≥6 points and/or mechanical recanalization)]. We assessed functional outcome by telephone interview 3 months (±14 days) after stroke using the 7-point modified Rankin Scale (mRS). Poor outcome was defined as mRS ≥3. Systemic plasma levels of S100A8/A9 were determined by ELISA <48 h after onset of symptoms, alongside a differential blood count. Univariable and multivariable logistic regression were performed to investigate the association between systemic plasma levels of S100A8/A9 and functional outcome. Results: Between June 2020 and September 2022, a total of 272 patients were enrolled [52 % female, median age 79 years (IQR: 66–84), median NIHSS score on admission 13 (IQR: 8–17), median ASPECTS 8 (IQR: 6–9)]. Of these, 220 patients (81 %) underwent mechanical recanalization, and 118 (43 %) received systemic thrombolytic therapy. There was a significant correlation between systemic plasma levels of S100A8/A9 and neutrophil counts at baseline [p < 0.0001; r = 0.33 (95 % confidence interval: 0.22; 0.44)]. At 3 months, 192 of 272 (71 %) patients had poor functional outcome, who had significantly higher systemic plasma levels of S100A8/A9 at baseline [median: 525 ng/ml (IQR: 342–897)] than those with good functional outcome [397 ng/ml (IQR: 232–580); p = 0.001]. Furthermore, systemic plasma levels of S100A8/A9 at baseline were associated with poor outcome [unadjusted odds ratio (OR): 2.01 (95 %CI: 1.04–3.96)], however this association was attenuated and no longer significant when adjusting for age, sex, NIHSS Score on admission, ASPECT Score on admission and recanalization therapy (yes/no) [adjusted OR: 1.92 (95 %CI: 0.86–4.34)]. Conclusions: Systemic plasma levels of S100A8/A9 were associated with poor outcome in patients with moderate to severe ischemic stroke. The observed correlation with neutrophil counts at baseline might underscore an important pathophysiological link between patients’ prognosis and stroke-related inflammation. Study registration: DRKS00022064. |
| format | Article |
| id | doaj-art-73088f28d0334ba1945ffbd41ecd4e57 |
| institution | Kabale University |
| issn | 2666-3546 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
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| series | Brain, Behavior, & Immunity - Health |
| spelling | doaj-art-73088f28d0334ba1945ffbd41ecd4e572025-08-20T03:31:34ZengElsevierBrain, Behavior, & Immunity - Health2666-35462025-08-014710104110.1016/j.bbih.2025.101041Systemic S100A8/A9 in patients with moderate to severe acute ischemic stroke: Exploratory analysis of inflammation and functional outcomeChristoph Vollmuth0Felipe A. Montellano1Cornelia Fiessler2Fabian Essig3Christian Hametner4Alexander M. Kollikowski5Vivian Vogt6Mirko Pham7Peter U. Heuschmann8Karl Georg Haeusler9Guido Stoll10Hermann Neugebauer11Michael K. Schuhmann12University Hospital Würzburg (UKW), Department of Neurology, Würzburg, Germany; Corresponding author.Department of Neurology, University Hospital Würzburg Josef-Schneider-Str. 11, 97080 Würzburg. GermanyUniversity Hospital Würzburg (UKW), Department of Neurology, Würzburg, Germany; University of Würzburg, Institute for Clinical Epidemiology and Biometry, Würzburg, GermanyUniversity of Würzburg, Institute for Clinical Epidemiology and Biometry, Würzburg, GermanyUniversity Hospital Würzburg (UKW), Department of Neurology, Würzburg, GermanyUniversity Hospital Würzburg (UKW), Department of Neurology, Würzburg, GermanyUniversity Hospital Würzburg (UKW), Department of Neuroradiology, Würzburg, GermanyUniversity Hospital Würzburg (UKW), Department of Neurology, Würzburg, GermanyUniversity Hospital Würzburg (UKW), Department of Neuroradiology, Würzburg, GermanyUniversity of Würzburg, Institute for Clinical Epidemiology and Biometry, Würzburg, Germany; Institute for Medical Data Science, University Hospital Würzburg, Germany; Clinical Trial Centre, University Hospital Würzburg, GermanyUniversity Hospital Ulm, Department of Neurology, Ulm, GermanyInstitute of Experimental Biomedicine I, University Hospital Würzburg, GermanyUniversity Hospital Würzburg (UKW), Department of Neurology, Würzburg, GermanyUniversity Hospital Würzburg (UKW), Department of Neurology, Würzburg, GermanyIntroduction: S100A8/A9, a danger-associated molecular pattern (DAMP), is released from leukocytes, mainly neutrophils, and augments inflammation and tissue damage. The role of systemic plasma levels of S100A8/A9 in stroke-related inflammation and its association with clinical outcome lacks sufficient data. Methods: Prospective, monocentric, observational study including patients with moderate to severe acute ischemic anterior circulation stroke [National Institutes of Health Stroke Scale (NIHSS) score ≥6 points and/or mechanical recanalization)]. We assessed functional outcome by telephone interview 3 months (±14 days) after stroke using the 7-point modified Rankin Scale (mRS). Poor outcome was defined as mRS ≥3. Systemic plasma levels of S100A8/A9 were determined by ELISA <48 h after onset of symptoms, alongside a differential blood count. Univariable and multivariable logistic regression were performed to investigate the association between systemic plasma levels of S100A8/A9 and functional outcome. Results: Between June 2020 and September 2022, a total of 272 patients were enrolled [52 % female, median age 79 years (IQR: 66–84), median NIHSS score on admission 13 (IQR: 8–17), median ASPECTS 8 (IQR: 6–9)]. Of these, 220 patients (81 %) underwent mechanical recanalization, and 118 (43 %) received systemic thrombolytic therapy. There was a significant correlation between systemic plasma levels of S100A8/A9 and neutrophil counts at baseline [p < 0.0001; r = 0.33 (95 % confidence interval: 0.22; 0.44)]. At 3 months, 192 of 272 (71 %) patients had poor functional outcome, who had significantly higher systemic plasma levels of S100A8/A9 at baseline [median: 525 ng/ml (IQR: 342–897)] than those with good functional outcome [397 ng/ml (IQR: 232–580); p = 0.001]. Furthermore, systemic plasma levels of S100A8/A9 at baseline were associated with poor outcome [unadjusted odds ratio (OR): 2.01 (95 %CI: 1.04–3.96)], however this association was attenuated and no longer significant when adjusting for age, sex, NIHSS Score on admission, ASPECT Score on admission and recanalization therapy (yes/no) [adjusted OR: 1.92 (95 %CI: 0.86–4.34)]. Conclusions: Systemic plasma levels of S100A8/A9 were associated with poor outcome in patients with moderate to severe ischemic stroke. The observed correlation with neutrophil counts at baseline might underscore an important pathophysiological link between patients’ prognosis and stroke-related inflammation. Study registration: DRKS00022064.http://www.sciencedirect.com/science/article/pii/S2666354625000997Blood-based biomarkerS100A8/A9CalprotectinInflammationPrognosisDanger-associated molecular patterns |
| spellingShingle | Christoph Vollmuth Felipe A. Montellano Cornelia Fiessler Fabian Essig Christian Hametner Alexander M. Kollikowski Vivian Vogt Mirko Pham Peter U. Heuschmann Karl Georg Haeusler Guido Stoll Hermann Neugebauer Michael K. Schuhmann Systemic S100A8/A9 in patients with moderate to severe acute ischemic stroke: Exploratory analysis of inflammation and functional outcome Brain, Behavior, & Immunity - Health Blood-based biomarker S100A8/A9 Calprotectin Inflammation Prognosis Danger-associated molecular patterns |
| title | Systemic S100A8/A9 in patients with moderate to severe acute ischemic stroke: Exploratory analysis of inflammation and functional outcome |
| title_full | Systemic S100A8/A9 in patients with moderate to severe acute ischemic stroke: Exploratory analysis of inflammation and functional outcome |
| title_fullStr | Systemic S100A8/A9 in patients with moderate to severe acute ischemic stroke: Exploratory analysis of inflammation and functional outcome |
| title_full_unstemmed | Systemic S100A8/A9 in patients with moderate to severe acute ischemic stroke: Exploratory analysis of inflammation and functional outcome |
| title_short | Systemic S100A8/A9 in patients with moderate to severe acute ischemic stroke: Exploratory analysis of inflammation and functional outcome |
| title_sort | systemic s100a8 a9 in patients with moderate to severe acute ischemic stroke exploratory analysis of inflammation and functional outcome |
| topic | Blood-based biomarker S100A8/A9 Calprotectin Inflammation Prognosis Danger-associated molecular patterns |
| url | http://www.sciencedirect.com/science/article/pii/S2666354625000997 |
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