Humoral immune response to Shiga Toxin 2 (Stx2) among Brazilian urban children with hemolytic uremic syndrome and healthy controls.

Mirian Guirro,Roxane Maria Fontes Piazza,Beatriz Ernestina Cabilio Guth,Renato Lopes De Souza

doi:10.1186/1471-2334-14-320

Mirian Guirro, Roxane Maria Fontes Piazza + Show 2 more

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https://doi.org/10.1186/1471-2334-14-320

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Abstract

BackgroundShiga toxin (Stx)-producing Escherichia coli (STEC) infection is associated with hemolytic uremic syndrome (HUS), the main cause of acute renal failure in early childhood. Stx is essential in the pathogenesis of HUS, which has been mostly related to Stx2-producing isolates. Very limited data exist on the immune response to STEC in the Brazilian population. In this study, the prevalence of immunoglobulin G (IgG) antibodies to Stx2 was investigated in sera of children diagnosed with HUS and of healthy children in the city of São Paulo, Brazil.MethodsIgG-antibody reactivity to Stx2 was determined by immunoblotting (WB) and enzyme-linked immunosorbent assay (ELISA) in sera from 13 children with HUS aged 8 months to 6 years and 54 healthy urban children aged 5 months to 7 years.ResultsA positive immune response to the A and B subunits of Stx2 was observed in 46.1% HUS patients and in 16.6% healthy individuals by WB. All HUS patients and 62.9% healthy children showed IgG antibodies to the Stx2 A subunit. The frequency of antibodies to both subunits or only to the A subunit of Stx2 was significantly higher in HUS patients than controls (p < 0.05). Also, the mean OD value obtained by ELISA was higher in that group. Considering children’s age, the frequency of reactivity to either the A subunit or both subunits of Stx2 was considerably higher in HUS children up to three years old compared to controls in the same age range. Moreover, in almost 37% of healthy children, no immune response to Stx2 was detected independently of the child’s age.ConclusionsThe seroepidemiolgy of anti-Stx2 antibodies was described for the first time in healthy children and children with HUS in Brazil. The percentage of individuals showing antibodies against Stx2 was higher among HUS patients than controls, and in spite of the low number of notified HUS cases, STEC strains are circulating in our settings. In addition, the results obtained also corroborated previous data on the increased sensitivity and specificity of WB compared to toxin-based enzyme immunoassays.

Highlights

Shiga toxin (Stx)-producing Escherichia coli (STEC) infection is associated with hemolytic uremic syndrome (HUS), the main cause of acute renal failure in early childhood
The immunoglobulin G (IgG) reactivity profile was first analyzed by Western blot (WB), and a positive immune response to the A and B subunits of Stx2 was observed in six (46.1%) HUS patients and nine (16.6%) healthy individuals (Figure 1A)
All 13 HUS patients and 34 (62.9%) healthy children showed IgG antibodies to the Stx2 A subunit

Summary

Introduction

Shiga toxin (Stx)-producing Escherichia coli (STEC) infection is associated with hemolytic uremic syndrome (HUS), the main cause of acute renal failure in early childhood. Shiga toxin-producing Escherichia coli (STEC) infection can induce hemolytic uremic syndrome (HUS), a thrombotic microangiopathy characterized by acute renal failure, thrombocytopenia and hemolytic anemia. O157:H7 is the most prominent STEC serotype implicated in serious outbreaks and sporadic cases of HUS. The toxin family contains two major groups that are serologically distinct, called Stx and Stx. The toxin family contains two major groups that are serologically distinct, called Stx and Stx2 The latter has multiple subtypes or variants in a range of combinations [13]. Among the Stx produced by human STEC isolates, Stx and Stx2c show the highest association with severe cases of HUS [14,15,16]

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