Elevated Serum High-Mobility Group Box-1 Protein Level Is Associated with Poor Functional Outcome in Ischemic Stroke

J Stroke Cerebrovasc Dis. 2017 Oct;26(10):2404-2411. doi: 10.1016/j.jstrokecerebrovasdis.2017.05.033. Epub 2017 Jun 20.

Abstract

Background: In experimental models, inhibition of high-mobility group box-1 (HMGB1) signaling has been reported to protect against the sequelae of ischemic stroke. Here, we determined the clinical significance of serum HMGB1 levels in patients with acute ischemic stroke.

Methods: We enrolled 183 patients (114 men, 69 women; mean age: 72.7 years) over 6 consecutive months. On admission and day 7, we recorded the National Institutes of Health Stroke Scale scores and measured serum high-sensitivity C-reactive protein (hs-CRP) and HMGB1 levels. Stroke volumes were estimated using diffusion-weighted magnetic resonance imaging performed on admission. One year later, clinical outcome was assessed using the modified Rankin Scale (mRS).

Results: Serum hs-CRP and HMGB1 levels in patients with ischemic stroke were increased relative to healthy controls (both P < .01). On day 7, hs-CRP, but not HMBG1, levels had increased significantly relative to levels at admission (P < .01 and .54, respectively). Higher HMGB1, but not hs-CRP, levels at day 7 correlated with larger stroke volumes (P < .01 and .28, respectively). HMGB1 levels did not significantly differ between stroke subtypes. Multiple logistic regression analysis indicated that a serum HMGB1 level higher than 7.5 ng/mL was an independent risk factor for poor prognosis, defined as a 1-year mRS score of 3-6 (odds ratio, 2.34; 95% confidence interval, 1.02-5.38).

Conclusions: Acute ischemic stroke is associated with elevated serum HMGB1 levels, and HMGB1 levels at admission independently predict poor outcome at 1 year. These results suggest that HMGB1 quantification provides more accurate prognostic information after ischemic stroke.

Keywords: HMGB proteins; Prognosis; cerebral infarction; cerebral ischemia; inflammation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Brain / diagnostic imaging
  • Brain Ischemia / blood*
  • Brain Ischemia / diagnostic imaging
  • C-Reactive Protein / metabolism
  • Diffusion Magnetic Resonance Imaging
  • Female
  • Follow-Up Studies
  • HMGB1 Protein / blood*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Prognosis
  • Severity of Illness Index
  • Stroke / blood*
  • Stroke / diagnostic imaging

Substances

  • Biomarkers
  • HMGB1 Protein
  • HMGB1 protein, human
  • C-Reactive Protein