Escherichia coli is the most common cause of urinary tract infections, which in some patients ascends to the kidneys and enters the bloodstream (urosepsis). Antibodies in sera usually act to defend against infections, but studies into other Gram-negative bacteria have identified patients expressing antibodies capable of inhibiting complement-mediated killing (Wells et al, 2014). These inhibitory antibodies were characterised as IgG2 specific to the O-antigen component of lipopolysaccharide (LPS) coating the bacteria surface. It was hypothesised that patients suffering with urosepsis may express O-antigen specific IgG2 antibodies capable of inhibiting the serum-mediated killing of E. coli, promoting progression of pathology.
45 patients with E. coli infection and urosepsis were screened for the presence of IgG2 specific for their cognate strain’s LPS. LPS extractions were confirmed by silver staining. Specific antibody titres were measured by ELISA. The complement-mediated inhibition was confirmed by serum bactericidal assays.
Over half the patients had detectable titres of IgG2 specific for the O-antigen region of LPS. Eleven patients had titres high enough to inhibit complement-mediated killing of E. coli isolates by Healthy Control Serum (HCS). These eleven isolates were statistically more sensitive to HCS than isolates cultured from patients without inhibitory antibody.
This suggests the presence of inhibitory antibody may be an important factor in progression of urinary tract infections to sepsis and could provide the basis for improved patient outcome via detection of inhibitory antibodies and subsequent treatment development.