Glycoproteins for serology in STEC-HUS: a closer look to a novel approach

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

Glasgow

Conferencia; 50th Anniversary of the European Society of Pediatric Nephrology Meeting; 2017

ESPN

Differentiation between Shiga toxin producing Escherichia coli (STEC) and atypical hemolytic uremic syndrome (HUS) is essential prior to start of treatment, as treatment of atypical HUS (aHUS) comprises one of world?s most expensive drugs nowadays: eculizumab. Furthermore, since aHUS is merely a diagnosis per exclusionem, providing proof for the presence of STEC forms the basis for differentiation between aHUS and STEC-HUS. However, the current golden standard (i.e. fecal diagnostics) to demonstrate STEC infection appears far from ideal. Serological detection of antibodies against the lipopolysaccharides (LPS) of STEC by ELISA has improved STEC-HUS diagnostics significantly. Yet, this assay revealed multiple limitations, whereas new techniques show promising results. Here we evaluate the use of serotype specific recombinant glycoproteins as antigens in a novel established glyco-iELISA. MethodsIn this retrospective study, all patients (n=61), who presented with clinical STEC-HUS in the Radboudumc between 1990-2014 were included. Serological assays using LPS and glyco-iELISA to detect IgM against STEC most common serotype O157 were compared to each other as well as to fecal diagnostics.ResultsBy the sole use of fecal diagnostics, 32 (53%) of the patients were diagnosed with an STEC infection. In total, 39 (65%) and 46 (75%) patients were diagnosed with STEC infection with respectively LPS-ELISA and glyco-iELISA. Moreover, fecal diagnostics failed to detect 20 of the 46 patients positive with glyco-iELISA. With LPS-ELISA, 7 patients went undetected when compared to glyco-iELISA.Combining the glyco-iELISA with fecal diagnostics provided evidence for STEC infection in 89% of the patients. ConclusionsThe novel glyco-iELISA is a sensitive and accurate serological method to detect STEC-HUS. This together with the stability, reliability and the absence of cross-reactivity places the glyco-iELISA ahead of the LPS- ELISA. Combined with fecal diagnostics, the glyco-iELISA improves the STEC detection by 36%.