Glyco-iELISA: a highly sensitive and unambiguous serological method to diagnose STEC-HUS caused by serotype O157

Pediatr Nephrol. 2019 Apr;34(4):631-639. doi: 10.1007/s00467-018-4118-9. Epub 2018 Oct 26.

Abstract

Background: Providing proof of presence of Shiga toxin-producing E. coli (STEC) infection forms the basis for differentiating STEC-hemolytic uremic syndrome (HUS) and atypical HUS. As the gold standard to diagnose STEC-HUS has limitations, using ELISA to detect serum antibodies against STEC lipopolysaccharides (LPS) has proven additional value. Yet, conventional LPS-ELISA has drawbacks, most importantly presence of cross-reactivity due to the conserved lipid A part of LPS. The newly described glyco-iELISA tackles this issue by using modified LPS that eliminates the lipid A part. Here, the incremental value of glyco-iELISA compared to LPS-ELISA is assessed.

Methods: A retrospective study was performed including all pediatric patients (n = 51) presenting with a clinical pattern of STEC-HUS between 1990 and 2014 in our hospital. Subsequently, the diagnostic value of glyco-iELISA was evaluated in a retrospective nationwide study (n = 264) of patients with thrombotic microangiopathy (TMA). LPS- and glyco-iELISA were performed to detect IgM against STEC serotype O157. Both serological tests were compared with each other and with fecal diagnostics.

Results: Glyco-iELISA is highly sensitive and has no cross-reactivity. In the single-center cohort, fecal diagnostics, LPS-ELISA, and glyco-iELISA identified STEC O157 infection in 43%, 65%, and 78% of patients, respectively. Combining glyco-iELISA with fecal diagnostics, STEC infection due to O157 was detected in 89% of patients. In the nationwide cohort, 19 additional patients (8%) were diagnosed with STEC-HUS by glyco-iELISA.

Conclusion: This study shows that using glyco-iELISA to detect IgM against STEC serotype O157 has clear benefit compared to conventional LPS-ELISA, contributing to optimal diagnostics in STEC-HUS.

Keywords: Glycoproteins; Hemolytic uremic syndrome; Serology; Shiga toxin–producing E. coli.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Bacterial / blood*
  • Biomarkers / blood
  • Enzyme-Linked Immunosorbent Assay*
  • Escherichia coli Infections / blood
  • Escherichia coli Infections / diagnosis*
  • Escherichia coli Infections / microbiology
  • Escherichia coli O157 / immunology*
  • Female
  • Hemolytic-Uremic Syndrome / blood
  • Hemolytic-Uremic Syndrome / diagnosis*
  • Hemolytic-Uremic Syndrome / microbiology
  • Humans
  • Immunoglobulin M / blood*
  • Male
  • Middle Aged
  • Netherlands
  • O Antigens / immunology*
  • Pilot Projects
  • Predictive Value of Tests
  • Reproducibility of Results
  • Retrospective Studies
  • Serologic Tests*
  • Young Adult

Substances

  • Antibodies, Bacterial
  • Biomarkers
  • Immunoglobulin M
  • O Antigens