Abstract
The specific anti-O polysaccharide antibody response in Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) patients and its relevance for early diagnosis have not been previously studied in detail. In this pre-planned post hoc analysis, we evaluated the IgM/IgG antibody response in 55 patients monitored since the date of clinical STEC-HUS diagnosis. Four serum samples per patient were collected at 12-24 h (T1), 48 h after T1, and 7 and 28 days post-STEC-HUS diagnosis. The serogroup-specific anti-O polysaccharide antibody response was evaluated by the glycoprotein-based assays. E. coli O157, O145, O121, O103, O111, O26, and O45 Glyco-iELISAs and the lateral flow immunoassay (LFIA) CHEMSTRIPE. coli O157/O145 and three IgM/IgG response patterns were observed. Analysis of the serum samples at T1 by Glyco-iELISAs and the LFIA revealed an overall reactivity of 89.1% (49/55), a value significantly higher than those obtained by stx/Stx detection (74%, 37/50) and stool culture (16.3%, 9/55). When combining all methodologies, the association with STEC infection was 96.4% (53/55). In samples ranging from 2 to 5 days post-diarrhea onset, the reactivity by serology, stx/Stx detection, and stool culture was 77.8%, 73.1%, and 25.9%, respectively, but when combining all the methodologies, it increased to 92.6%. The detection of serogroup-specific anti-O polysaccharide antibodies alone or in combination with fecal diagnostics significantly contributed to STEC diagnosis in HUS patients, even very early in the course of the infection. These findings strongly support the incorporation of serology into diagnostic algorithms for timely diagnosis and proper management of STEC-HUS patients. IMPORTANCE: This study evaluated, for the first time, the dynamics of serogroup-specific IgM and IgG anti-O polysaccharide antibody response in 55 Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) pediatric patients. We provide evidence that the detection of serogroup-specific anti-O polysaccharide antibodies alone or in combination with bacterial isolation and/or stx/Stx detection from stool samples significantly contributes to STEC diagnosis in HUS patients in the first days after the onset of diarrhea. This could potentially improve the way we currently diagnose these infections. Our glycoprotein-based serological tests could be incorporated into diagnostic algorithms and implemented in primary care settings upon presentation of bloody or non-bloody diarrhea, enabling rapid and simple screening without the need for invasive procedures. This could allow the timely identification of these potentially harmful infections and close monitoring of these patients or help refer them to tertiary-care hospitals for proper clinical management. CLINICAL TRIALS: This study was registered with ClinicalTrials.gov as NCT05569746.