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Tissue markers may predict treatment response to antitumor necrosis factor-α agents in children with Crohn's disease
Alexander Krauthammer1,2, Tal Cozacov1,3, Sophia Fried1,3
1Schneider Children's Medical Center of Israel, Institute of Gastroenterology, Nutrition and Liver Diseases, Petah Tikva, Israel.
Insights
Tissue markers like fibronectin, collagen III, and TNF-α may predict response to anti-tumor necrosis factor alpha (TNF-α) therapy in Crohn's disease patients. Lower fibronectin and collagen III, with higher TNF-α, indicate better treatment response.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Crohn's disease (CD) patients treated with anti-tumor necrosis factor alpha (TNF-α) agents often experience primary nonresponse or partial response.
- Identifying predictive tissue markers is crucial for optimizing anti-TNF-α therapy in moderate-to-severe CD.
Purpose of the Study:
- To identify specific tissue markers that can predict treatment response in pediatric patients with moderate-to-severe CD receiving anti-TNF-α agents.
- To stratify patients based on their response to anti-TNF-α therapy and analyze tissue marker expression.
Main Methods:
- Pediatric CD patients (6-18 years) were stratified into full responders (FR), partial responders (PR), and nonresponders (NR) based on clinical and laboratory parameters.
- Immunofluorescence (IF) analyses were performed on terminal ileum biopsies to evaluate seven tissue markers: fibronectin, IL-23R, IL-23, TNF-α, collagen-III, IL-13R, and HIF-1α.
- Biopsies were obtained up to six months prior to treatment initiation.
Main Results:
- Significant differences in tissue marker expression were observed between nonresponders (NR) and full responders (FR).
- Collagen III and fibronectin tissue staining were significantly more prominent in NR patients compared to FR patients.
- TNF-α tissue staining was significantly more pronounced in FR patients than in NR patients (p < 0.05 for all significant findings).
- Partial response (PR) could not be predicted by any of the evaluated markers.
Conclusions:
- Decreased tissue immunofluorescence intensity of fibronectin and collagen III may predict a lack of response to anti-TNF-α treatment.
- Increased tissue immunofluorescence intensity of TNF-α may predict a positive response to anti-TNF-α treatment in Crohn's disease.
- These markers could aid in personalizing anti-TNF-α therapy selection for CD patients.
Objectives:
Patients with moderate-severe Crohn's disease (CD) who are treated with antitumor necrosis factor alpha (TNF-α) agents may be subjected to primary nonresponse or partial response. We aimed to identify tissue markers that may predict response to these agents.
Methods:
Pediatric patients (6-18 years) with either ileal or ileo-colonic CD who were treated with anti-TNF-α were stratified into three different groups based on their overall response to therapy at the end of induction including clinical and laboratory parameters (group 1-full responders [FR], group 2-partial responders [PR], group 3-nonresponders [NR]). Seven tissue markers (fibronectin, interleukin [IL]-23R, IL-23, TNF-α, collagen-III, IL-13R, and hypoxia-inducible factors [HIF]-1α) were evaluated. Immunofluorescence (IF) analyses were performed on biopsies from the terminal ileum, which were retrieved up to 6 months before treatment initiation.
Results:
Twenty-six CD patients (16 [61.5%] males; age 13.9 ± 2.9 years), including 8 (30.8%) with ileal disease and 18 (69.2%) with ileo-colonic disease, were enrolled. Terminal ileum biopsies from nine patients from group 1, nine from group 2, and eight from group 3 were evaluated. Three antibodies were found to be significantly different between NR and FR groups; Collagen III and fibronectin stains were significantly more prominent in NR patients, while TNF-α stain was significantly more pronounced in FR, p < 0.05 for each. PR could not have been predicted with neither of markers.
Conclusions:
Decreased tissue IF intensity of fibronectin and collagen III and increased intensity of TNF-α may predict response to anti-TNF-α treatment.
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