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A Protein Microarray Assay for Serological Determination of Antigen-specific Antibody Responses Following Clostridium difficile Infection
Published on: June 15, 2018
Clostridium difficile carriage and serum antitoxin responses in children with inflammatory bowel disease
Suchitra K Hourigan1, Sankar R Chirumamilla, Tracy Ross
1*Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Maryland; †Department of Physical Medicine and Rehabilitation, University of Kentucky, Lexington, Kentucky; ‡Department of Molecular Microbiology and Epidemiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland; §Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland; ‖Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cedars-Sinai Hospital, Los Angeles, California; ¶Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; **Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; ††Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; ‡‡Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland; and §§Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Insights
Pediatric inflammatory bowel disease (IBD) patients show higher Clostridium difficile carriage and antibody responses. Proton pump inhibitor use was linked to increased carriage in these children.
Area of Science:
- Pediatric Gastroenterology
- Infectious Diseases
- Microbiology
Background:
- Inflammatory bowel disease (IBD) affects children, with limited data on Clostridium difficile (C. diff) carriage.
- C. diff toxin antibody responses in pediatric IBD patients are not well-described.
Purpose of the Study:
- To determine C. diff carriage prevalence in pediatric IBD outpatients.
- To compare serum antibody responses to C. diff toxins between pediatric IBD patients and controls.
Main Methods:
- Prospective collection of fecal and serum samples from 85 pediatric IBD patients and 78 controls.
- C. diff detection via culture and PCR for toxin B gene; strain typing by pulsed-field gel electrophoresis.
- Serum immunoglobulin responses to C. diff toxins measured by ELISA.
Main Results:
- Asymptomatic C. diff carriage was significantly higher in IBD patients (17%) than controls (3%).
- Proton pump inhibitor use was associated with increased C. diff carriage (54% vs. 25%).
- IBD patients showed a greater proportion of positive serum antibody responses to C. diff toxin A (69% vs. 53%).
Conclusions:
- Asymptomatic toxigenic C. diff carriage is increased in pediatric IBD outpatients.
- Proton pump inhibitor use is a potential risk factor for C. diff carriage in this population.
- Elevated antibody responses in IBD may promote asymptomatic C. diff colonization; further research on symptomatic C. diff risk factors is needed.
Background:
Adults with inflammatory bowel disease (IBD) have a high prevalence of Clostridium difficile carriage, but little data exist regarding pediatric patients with IBD. Serum antibody responses to C. difficile toxins in correlation with organism carriage are not described in IBD. This study determines the prevalence of C. difficile carriage and compares serum antibody responses to C. difficile toxins in pediatric outpatients with IBD and controls.
Methods:
Fecal and serum samples were prospectively collected from pediatric outpatients with IBD (n = 85) and age-matched controls (n = 78). Initial and follow-up stool samples were tested using cytotoxigenic C. difficile culture and PCR to detect the toxin B gene. Pulsed-field gel electrophoresis determined the strain type. Enzyme-linked immunosorbent assay determined serum immunoglobulin responses to C. difficile toxins.
Results:
Asymptomatic C. difficile carriage was significantly greater in IBD (17%) versus controls (3%) (P = 0.012). IBD type, disease severity, IBD therapy, recent antibiotics, and hospitalizations were not associated with carriage. Proton pump inhibitor use was significantly higher in patients with C. difficile carriage (54% versus 25%, P < 0.05). North American pulsed-field (NAP) strain carriage varied over time in patients colonized with C. difficile. A significantly greater proportion of patients with IBD had a positive serum antibody response to toxin A (69%) compared with controls (53%) (P < 0.05).
Conclusions:
Asymptomatic toxigenic C. difficile carriage was increased in pediatric outpatients with IBD compared with controls. Proton pump inhibitor use was associated with increased carriage. Antibody responses to C. difficile toxins were increased in IBD, potentially promoting asymptomatic colonization. Future studies should identify the risk factors for symptomatic C. difficile in pediatric IBD.
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