Glyco-iELISA: on the horizon of STEC-HUS diagnostics

VEISI S; KIOA L. WIJNSMA ; JUAN E. UGALDE ; COMERCI D. J; NICOLE C.A.J. VAN DE KAR; LAMBERTUS P. VAN DEN HEUVEL

New Orleans

Congreso; ASN 2017; 2017

American Society of Nephrology

ObjectivesDistinguishment between hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC-HUS) or a dysregulated complement system (atypical HUS; aHUS) is a clinical conundrum. As aHUS - whose treatment requires the highly expensive drug eculizumab - is diagnosed per exclusionem, a method to reliably detect STEC infection is warranted. Since the current golden standard (fecal diagnostics; FD) for the detection of STEC infection has important drawbacks, the serological detection of antibodies against STEC-associated lipopolysaccharides by enzyme-linked immunosorbent assays (LPS-ELISA) has proven its value. However, LPS-based ELISAs have important limitations. Therefore, we have developed and evaluated the diagnostic value of ELISAs employing recombinant glycoproteins of STEC-associated lipopolysaccharides (glyco-iELISA). MethodsIn this retrospective study, patients (n=61) who presented with clinical STEC-HUS in the Radboudumc between 1990-2014 were included. Clinical, diagnostic and follow up data were gathered. LPS-ELISAs and glyco-iELISAs were employed to detect IgM and IgG antibodies against the most common serotype of STEC (O157). ResultsFD, LPS-ELISAs, or glyco-iELISAs identified STEC infection in 53%, 74%, and 77% of patients, respectively. The glyco-iELISA proved STEC infection in 3 (5%) and 20 (33%) additional patients when compared to the LPS-ELISA or FD, respectively. Combining the glyco-iELISA with FD identified STEC infection in 90% of patients. The glyco-iELISA appeared highly reproducible and reliable, as the intra- and inter-assay variability was low. ConclusionThe glyco-iELISA is a highly sensitive and accurate serological method to detect STEC in HUS patients. Combined with FD, the glyco-iELISA improves STEC detection by 37%. Thus, the glyco-iELISA may drastically limit the unnecessary use of eculizumab in HUS.