Plasma Immunoproteasome Predicts Early Hemorrhagic Transformation in Acute Ischemic Stroke Patients

J Stroke Cerebrovasc Dis. 2017 Jan;26(1):49-56. doi: 10.1016/j.jstrokecerebrovasdis.2016.08.027. Epub 2016 Sep 14.

Abstract

Background and purpose: Currently, blood biomarkers associated with an increased hemorrhagic transformation (HT) risk remain uncertain. We aimed to determine the significance of immunoproteasome as predictors of early HT in acute ischemic stroke patients.

Methods: This study enrolled 316 patients with ischemic stroke. HT was assessed by computed tomography examination performed on day 5 ± 2 after stroke onset or immediately in case of clinical deterioration (CD). Plasma immunoproteasome subunits low molecular mass peptide 2 (LMP2), multicatalytic endopeptidase complex-like 1 (MECL-1), LMP7, interleukin-1β (IL1β), and high-sensitivity C-reactive protein (Hs-CRP) were measured with quantitative sandwich enzyme-linked immunosorbent assay kits. Factors associated with HT were analyzed using a multivariate logistic regression analysis.

Results: There were 42 (13.3%, 42 of 316) patients who experienced HT. Compared with those patients without HT, plasma LMP2, MECL-1, LMP7, IL1β, and Hs-CRP concentrations on admission were significantly increased in patients with subsequent HT (P < .001). These protein concentrations increased with hemorrhage severity. Patients with CD caused by HT had the highest levels of LMP2 (1679.5 [1394.6-136.6] pg/mL), MECL-1 (992.5 [849.7-1075.8] pg/mL), LMP7 (822.6 [748.6-1009.5] pg/mL), IL1β (113.2 [90.6-194.5] pg/mL), and Hs-CRP (30.0 [12.8-75.6] mg/L) (P < .05). Logistic regression analysis showed cardioembolism, LMP2, MECL-1, and LMP7 as independent predictors of HT (P < .05). Receiver operating characteristic curve analysis demonstrated LMP2 ≥ 988.3 pg/mL, MECL-1 ≥ 584.7 pg/mL, and LMP7 ≥ 509.0 pg/mL as independent factors associated with HT (P < .001).

Conclusion: Evaluation of plasma levels of immunoproteasome could be helpful in the early prediction of HT in acute ischemic stroke patients.

Keywords: Immunoproteasome; cerebral infarction; hemorrhagic transformation; risk factors.

MeSH terms

  • Aged
  • Brain Ischemia / complications
  • C-Reactive Protein / metabolism
  • Cysteine Endopeptidases / blood
  • Cytokines / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoproteins / metabolism*
  • Intracranial Hemorrhages / blood*
  • Intracranial Hemorrhages / diagnosis*
  • Intracranial Hemorrhages / etiology*
  • Logistic Models
  • Male
  • Middle Aged
  • Proteasome Endopeptidase Complex / blood*
  • Stroke / complications*
  • Stroke / etiology

Substances

  • Cytokines
  • Immunoproteins
  • LMP-2 protein
  • C-Reactive Protein
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex