Upregulation of Shiga toxin receptor CD77/Gb3 and interleukin-1β expression in the brain of EHEC patients with hemolytic uremic syndrome and neurologic symptoms

Brain Pathol. 2015 Mar;25(2):146-56. doi: 10.1111/bpa.12166. Epub 2014 Sep 5.

Abstract

In 2011, a large outbreak of Shiga toxin-producing enterohemorrhagic Escherichia coli (EHEC) infections occurred in northern Germany, which mainly affected adults. Out of 3842 patients, 104 experienced a complicated course comprising hemolytic uremic syndrome and neurological complications, including cognitive impairment, aphasia, seizures and coma. T2 hyperintensities on magnet resonance imaging (MRI) bilateral in the thalami and in the dorsal pons were found suggestive of a metabolic toxic effect. Five of the 104 patients died because of toxic heart failure. In the present study, the post-mortem neuropathological findings of the five EHEC patients are described. Histological investigation of 13 brain regions (frontal, temporal, occipital cortex, corpora mammillaria, thalamus, frontal operculum, corona radiata, gyrus angularis, pons, medulla oblongata, cerebellar vermis and cerebellar hemisphere) showed no thrombosis, ischemic changes or fresh infarctions. Further, no changes were found in electron microscopy. In comparison with five age-matched controls, slightly increased activation of microglia and a higher neuronal expression of interleukin-1β and of Shiga toxin receptor CD77/globotriaosylceramide 3 was observed. The findings were confirmed by Western blot analyses. It is suggested that CD77/globotriaosylceramide upregulation may be a consequence to Shiga toxin exposure, whereas increased interleukin-1β expression may point to activation of inflammatory cascades.

Keywords: CD77/Gb3; enterohemorrhagic Escherichia coli; hemolytic uremic syndrome; microglia; neuropathology; vasculature.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Brain / blood supply
  • Brain / metabolism*
  • Brain / microbiology
  • Brain / ultrastructure
  • Cognition Disorders / microbiology
  • Encephalitis / metabolism
  • Encephalitis / microbiology
  • Enterohemorrhagic Escherichia coli*
  • Escherichia coli Infections / metabolism*
  • Escherichia coli Infections / pathology
  • Female
  • Hemolytic-Uremic Syndrome / microbiology
  • Hemolytic-Uremic Syndrome / pathology*
  • Humans
  • Interleukin-1beta / metabolism*
  • Male
  • Trihexosylceramides / metabolism*
  • Up-Regulation

Substances

  • Interleukin-1beta
  • Trihexosylceramides
  • globotriaosylceramide