Profiling the systemic and gut anti-commensal antibody repertoire of children with IBD
2Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center
Background: inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is often accompanied by characteristic alterations in immune responses to gut microbiota. Previous studies have identified associations between plasma and stool antibodies against select commensal bacteria, but these typically investigated a limited panel of microbes and sampled patients at varying stages of the disease. Furthermore, most work on gut antibodies has focused on IgA bound to specific bacterial species, leaving the significance of unbound IgA and IgG antibodies in stool samples largely unexplored.
Methods: We enrolled 214 pediatric patients newly diagnosed with IBD (134 CD, 61 UC, and additional IBD subtypes). plasma was collected at the time of diagnosis, prior to treatment initiation. Stool samples were obtained from 60 CD and 20 UC patients within one week of diagnosis. Using antigen microarrays, we profiled IgG and IgA repertoires against a broad panel of bacterial and fungal species, in addition to antigens from common childhood vaccines and viruses. Antibody signals were quantified and normalized as geometric means for bacterial, fungal and viral antigen groups.
Results: We found that children with CD exhibit significantly higher baseline plasma IgG responses to bacterial (p>0.01) and fungal (p<0.01) antigens compared with those with UC.
To assess disease activity over time in CD, we employed the Weighted Pediatric Crohn’s Disease Activity Index (wPCDAI). This approach allowed us to distinguish treatment responders from non-responders as therapy progressed. Notably, patients who did not achieve remission (wPCDAI > 12.5), showed elevated antibody responses to several facultative anaerobe’s genera as compared to patients who achieved remission (wPCDAI <=12). Most prominently we found that lower IgG antibodies against Escherichia and Enterococcus at the time of diagnosis were associated with remission (p<0.01 and p<0.05, respectively).
Conclusion: Our findings indicate CD is characterized by heightened baseline plasma IgG responses to bacterial and fungal antigens, distinguishing it from UC. Furthermore, robust immune recognition of facultative anaerobes genera correlates with a lack of treatment-induced remission in CD. These results suggest that comprehensive profiling of antibodies in both plasma and stool may offer valuable biomarkers for disease severity and therapeutic outcomes in pediatric IBD.