Host Immune Response to Clostridium difficile Infection in Inflammatory Bowel Disease Patients

Abstract

Background Clostridium difficile infection affects IBD patients. This study’s aim was to compare humoral response to C. difficile toxins in IBD and control outpatients. Methods We prospectively followed adult IBD and control subjects with serum and stool tested by PCR obtained at enrollment and during periods of CDI. Semi-quantitative serum levels of IgM, IgG and IgA to C. difficile toxins A and B were measured. Results 119 stool and 117 serum samples were obtained from 150 subjects. Different levels of IgA to toxin A (p=0.0016) and toxin B (p=0.0468) were noted between different IBD groups. Toxin A IgA levels were higher in the CD group (p=0.0321) and IPAA group (p=0.001) compared to the UC group and toxin B IgA levels were higher in the IPAA group compared to the UC group (p=0.0309). There were lower levels of toxin A IgA in IBD patients with compared with those in subjects without new CDI (P=0.0488) and higher levels in IBD patients with compared with those in subjects without CDI history before enrollment (P=0.016). There were nonsignificant lower toxin A IgG levels in IBD patients with compared to without prior CDI (p=0.095) and higher levels in controls with history of prior CDI compared to IBD patients with prior CDI (p=0.049). Conclusions UC patients have lower IgA levels to C. difficile toxins compared to Crohn’s and IPAA patients. IBD patients with prior CDI failed to demonstrate any increase in anti-toxin IgG. Our findings suggest that IBD patients may benefit from immunization strategies targeting C. difficile toxins.

Humoral response to Clostridium difficile in inflammatory bowel disease, including correlation with immunomodulatory treatment

“…Both the incidence and severity of C. difficile infection have increased dramatically in the general population during the past two decades, and there has been an even higher increase among patients with IBD . The humoral immune response to the C. difficile toxins A and B is known to be protective in humans, but previous reports on seroreactivity to C. difficile in IBD patients have provided conflicting results . In summary, we found IgA levels in IBD to be no different from healthy controls but IgG to toxin A to be elevated similarly in both CD and UC and IgG to toxin B to be elevated only in CD.…”

“…Findings differing from ours may be attributed to inclusion of subjects with ongoing or recent C. difficile infection. Hughes et al . observed elevated IgA to both toxins in patients with infection and no IgG abnormalities in IBD; a strength of this study is more detailed clinical information than in our material, including ruling out a significant difference in antibiotic use during the prior 6 months between IBD patients and healthy controls.…”

“…A few IBD patients were included in a cystic fibrosis study, with a tendency for IgG to toxin A, but not to toxin B, to become generated during ongoing C. difficile infection . Another study failed to demonstrate any increase in antitoxin IgG due to C. difficile infection in IBD patients . Several factors may have contributed to these discrepant observations, such as patient characteristics involving remission, relapse, C. difficile infection (prior or ongoing), IBD treatment types, previous intestinal resection, and control subject characteristics as well as enzyme‐linked immunosorbent assay (ELISA) methodology.…”

Low Frequency of Opportunistic Infections in Patients Receiving Vedolizumab in Clinical Trials and Post-Marketing Setting

“…27, 28 The occurrence and severity of C. difficile infections in patients with IBD may in part relate to host factors such as immune response and changes in the gut microbiota. 29, 30 A recent case-control study found that the use of a TNF antagonist (not controlling for concomitant medications that included azathioprine or 6-mercaptopurine) was associated with an increased risk of opportunistic infection (odds ratio 4.4; 95% CI 1.1–17.0; P = 0.03), which may be due to systemic immunosuppression by TNF antagonists. 31 In addition, the risk of an opportunistic infection was found to be increased by the use of steroids in combination with other immunosuppressive agents.…”

Lemon Exosome-like Nanoparticles-Manipulated Probiotics Protect Mice from C. diff Infection

“…Besides the AhR-mediated pathway that protects mice from CDI, other pathways have been recognized as well for protection of mice from CDI, including innate and adaptive immune responses ( Hughes et al., 2016 ; Solomon, 2013 ). Our results showed that indole is a survival factor for C. diff and production of bacterial indole is inhibited by lactic acid induced by LELN-LS treatment.…”