Abstract
Background
Aberrant immune responses play a key role in the pathogenesis of inflammatory bowel disease (IBD). Most studies conducted to delineate the underlying molecular mechanisms focus on adults; an understanding of these mechanisms in children remains to be determined. Here, cytokines and transcription factors produced by immune cells within the intestinal mucosa of pediatric patients stricken with ulcerative colitis (UC) and Crohn’s disease (CD) are characterized; potential diagnostic and therapeutic targets are identified.
Methods
Fifty-two pediatric IBD and non-IBD patients were enrolled in the study. Specimens were taken during ileocolonoscopy. Expression of 16 genes that encode cytokines or transcription molecules was determined by quantitative polymerase chain reaction. Clinical data were collected via retrospective chart review.
Results
Overexpression of interleukin-17A (IL-17A) was evident in children with UC compared to both non-IBD and CD patients. IL-22 was strongly increased in UC patients only. Typical proinflammatory and immunoregulatory cytokines were pronounced in IBD patients, although to a lower extent in the latter case. Clustered gene expression enabled differentiation between UC and non-IBD patients.
Conclusion
Our findings highlight the crucial involvement of IL-17A immunity in the early course of IBD, particularly UC, and the potential value of gene panels in diagnosing pediatric IBD.
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Acknowledgements
Results shown in this study are part of the doctoral thesis of M.A.B. We thank Dr. Stephen H. Gregory (Providence, RI, USA) for his help writing and editing this manuscript. M.A.B. received a personal grant through the Sibylle Kalkhof-Rose Foundation.
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M.A.B. performed and analyzed experiments, interpreted the findings, and prepared the manuscript; R.L.K. supported acquisition of clinical data and critically revised the manuscript for important intellectual content; I.H. helped with the statistical analysis and graph editing; U.K and V.B. performed the endoscopies and collected tissue samples; A.D. performed tissue preparation; C.U.M., B.G., and L.P. supported the experiments and gave critical input to the project; F.Z. was involved in the study design and in the interpretation of the immunological findings; S.G. designed the study, acquired funding, collected tissue samples, and critically revised the manuscript for important intellectual content.
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Busch, M.A., Gröndahl, B., Knoll, R.L. et al. Patterns of mucosal inflammation in pediatric inflammatory bowel disease: striking overexpression of IL-17A in children with ulcerative colitis. Pediatr Res 87, 839–846 (2020). https://doi.org/10.1038/s41390-019-0486-5
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DOI: https://doi.org/10.1038/s41390-019-0486-5
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