Low levels of circulating IgG against bacterial GAPDH and elevated IL-10 levels are associated with increased susceptibility to Escherichia coli bacteraemia

BackgroundWhile antimicrobial resistance is an increasingly urgent problem, with Escherichia coli infections representing a major priority, the development of effective vaccines has proven both challenging and largely unsuccessful. Given accumulating evidence supporting the immunosuppressive role of extracellular bacterial glyceraldehyde-3-phosphate dehydrogenase (GAPDH), we aimed to characterize individual susceptibility to E. coli infections based on the presence of naturally induced antibodies against this protein. MethodsWe conducted an observational case-control study including 62 individuals with E. coli bacteraemia (cases) and 124 age- and sex-matched controls without infection. Detection of GAPDH was performed in plasma samples, and plasma interleukin (IL)-10 levels and anti-GAPDH IgG (titers and concentrations) were quantified. Associations between anti-GAPDH IgG levels and infection were evaluated using logistic regression, and individual disease risk was estimated with a multivariate model incorporating IL-10 detection and low levels of anti-GAPDH IgG. ResultsE. coli GAPDH was detected in the plasma of cases from which purified colonies of E. coli were isolated. IL-10 levels were significantly higher (p < 0.0001) in cases while anti-GAPDH IgG levels were significantly lower (p < 0.0001) comparing with controls. Logistic regression analysis revealed a strong inverse association between anti-GAPDH IgG and the diagnosis of E. coli bacteraemia (adjusted OR = 0.18, 95% CI 0.08-0.37) and a protective threshold of 1.0 g/mL was estimated, below which, 95.2% of cases were classified. In a multivariate logistic regression model, detection of IL-10 was strongly associated with infection risk (OR = 629, 95% CI 139-5355), while low anti-GAPDH IgG showed a trend towards increased risk (OR = 4.26, 95% CI 0.91-30.6). This model allowed the estimation of individual probabilities and absolute risk of E. coli bacteraemia using a combining biomarker based on levels of anti-GAPDH IgG and IL-10. ConclusionsThis study provides the first evidence in humans of the protective potential of circulating anti-GAPDH antibodies, which supports GAPDH as a promising target for an alternative vaccination strategy to prevent E. coli infections.