Previous studies suggest that there may be a defect in the control of immune responses locally in the intestines with inflammatory bowel disease (IBD).
Recently, Dr Thomas Kraus and colleagues documented a failure to induce oral tolerance to a fed soluble protein antigen in IBD patients.
The soluble protein antigen was keyhole limpet hemocyanin.
Both Crohn's disease and ulcerative colitis appear to be multigenic disorders with evidence of familial segregation.
The investigative team analyzed multiplex IBD families to determine whether the defect in oral tolerance induction is genetically regulated.
Patients and first-degree relatives from 6 multiplex families were fed the protein antigen 50 mg on days 0 to 5 and 10 to 15.
This was followed by subcutaneous immunizations on days 26 and 35.
The investigators obtained blood and analyzed for the antigen-specific T cell proliferative responses and cytokine production.
| Failure of tolerance induction could not be attributed to increased intestinal permeability|
|Inflammatory Bowel Disease|
The investigative team also assessed intestinal permeability.
In contrast to normal controls, all IBD patients, save 1, failed to develop oral tolerance to keyhole limpet heocyanin.
Furthermore, in 3 of the 4 Crohn's disease families, at least 1 unaffected family member also failed to tolerize.
The team noted that this was in sharp contrast to unaffected individuals with no family history of IBD.
Dr Kraus' team concluded, “This failure of tolerance induction could not be attributed to increased intestinal permeability.”
“In the ulcerative colitis families, the defect in tolerance segregated with disease.”
“These data support a genetic defect in tolerance induction in Crohn's disease.”