Data on the seroprevalence of antibodies to Clostridioides difficile surface proteins and
toxins are scarce.
In 1983, Viscidi et al. showed that antibodies to C. difficile toxins A and B were detected
in 60 to 70% of an adult population. Two-thirds of the adults tested had a serological trace,
probably linked to a previous encounter with C. difficile.
One of the hypotheses raised would be that exposure to this pathogen occurs very early and
regularly throughout our lives. Indeed, in this study, antibodies to C. difficile toxins were
detected from early childhood and persisted over time even after 60 years. The antibody
response did not appear to vary with age or terrain. However, these results were only
qualitative and did not allow for inter-individual variations due to the limitations of the
techniques used at the time. Finally, in this work, it was important to underline that the
neutralizing character of the cytotoxic effect of toxins on cell culture was not observed in
all patients.
Since this seminal work, several studies have shown that the host immune response plays a
central role in the pathophysiology of C. difficile infections (CDI). In 2000, Kyne et al.
showed that after colonization with a toxigenic C. difficile strain, patients with
asymptomatic carriage had significantly higher serum levels of IgG directed against toxin A
than patients who developed disease. Subsequently, they also showed in 2001 that a serum
response directed against toxin A after a first episode of CDI was associated with less
recurrence. Finally, Leav et al. showed in 2010 that a serum response directed against C.
difficile toxin B was also associated with protection against recurrent forms.
Several studies have also suggested that the host immune response, this time directed against
colonization factors, could also play a major role in the evolution and prognosis of CDI. In
a previous study, investigators showed a significant difference in the level of anti-SlpA
antibodies (S-layer component) between CDI patients and control patients.
At the same time, the epidemiology of CDI has changed since 2003 due to the emergence of a
new epidemic and hypervirulent strain (PCR ribotype 027) producing a third toxin, the binary
toxin. The humoral response to this toxin remains poorly described to date.
On the basis of these numerous studies, new therapeutic immunization strategies (active or
passive) aimed at neutralizing the action of C. difficile toxins and colonization factors
have been or are being developed.
However, it remains to identify the patients likely to benefit from these innovative
strategies. This was the main objective of the SERODIFF study (currently being finalized),
which identified certain patient profiles in which no seroconversion or isotype class
switching of antibodies was observed following CDI. The absence of neutralizing antibody
production would seem to correlate with recurrent forms. Thus, these patients would be those
who could be eligible for a passive immunization strategy such as the administration of
anti-toxin B monoclonal antibodies, bezlotoxumab, recently marketed in France.
In this study, investigators aim to evaluate the seroprevalence stratified by age group, sex
and by the main risk factors for CDI. Furthermore, the neutralizing and protective effect of
the detected antibodies against C. difficile virulence factors will be studied.