Cortney R Ballengee1, Ryan W Stidham2, Chunyan Liu3, Mi-Ok Kim4, Jarod Prince1, Kajari Mondal1, Robert Baldassano5, Marla Dubinsky6, James Markowitz7, Neal Leleiko8, Jeffrey Hyams9, Lee Denson10, Subra Kugathasan11. 1. Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Emory University, Atlanta, Georgia. 2. Department of Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan. 3. Division of Biostatistics & Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 4. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California. 5. Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of Pennsylvania, Philadelphia, Pennsylvania. 6. Department of Pediatrics, Division of Gastroenterology, Mount Sinai Hospital, New York, New York. 7. Department of Pediatrics, Division of Gastroenterology, Northwell Health, New York, New York. 8. Department of Pediatrics, Division of Gastroenterology, Nutrition, and Liver Diseases, Brown University, Providence, Rhode Island. 9. Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut. 10. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 11. Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Emory University, Atlanta, Georgia. Electronic address: skugath@emory.edu.
Abstract
BACKGROUND & AIMS: There are few serum biomarkers to identify patients with Crohn's disease (CD) who are at risk for stricture development. The extracellular matrix components, collagen type III alpha 1 chain (COL3A1) and cartilage oligomeric matrix protein (COMP), could contribute to intestinal fibrosis. We investigated whether children with inflammatory CD (B1) who later develop strictures (B2) have increased plasma levels of COL3A1 or COMP at diagnosis, compared with children who remain B1. We compared results with previously studied biomarkers, including autoantibodies against colony-stimulating factor 2 (CSF2). METHODS: We selected 161 subjects (mean age, 12.2 y; 62% male) from the Risk Stratification and Identification of Immunogenic and Microbial Markers of Rapid Disease Progression in Children with Crohn's cohort, completed at 28 sites in the United States and Canada from 2008 through 2012. The children underwent colonoscopy and upper endoscopy at diagnosis and were followed up every 6 months for 36 months; plasma samples were collected at baseline. Based on CD phenotype, children were separated to group 1 (B1 phenotype at diagnosis and follow-up evaluation), group 2 (B2 phenotype at diagnosis), or group 3 (B1 phenotype at diagnosis who developed strictures during follow-up evaluation). Plasma samples were collected from patients and 40 children without inflammatory bowel disease (controls) at baseline and analyzed by enzyme-linked immunosorbent assay to measure COL3A1 and COMP. These results were compared with those from a previous biomarker study. The Kruskal-Wallis test and the pairwise Dunn test with Bonferroni correction were used to compare differences among groups. RESULTS: The median baseline concentration of COL3A1 was significantly higher in plasma from group 3 vs group 1 (P < .01) and controls (P = .01). Median baseline plasma concentrations of COMP did not differ significantly among groups. A model comprising baseline concentrations of COL3A1 and anti-CSF2 identified patients with B2 vs B1 CD with an area under the curve of 0.80 (95% CI, 0.71-0.89); the combined concentration identified patients with strictures with a sensitivity value of 0.70 (95% CI, 0.55-0.83) and a specificity value of 0.83 (95% CI, 0.67-0.93). CONCLUSIONS: We found median plasma concentrations of COL3A1, measured by enzyme-linked immunosorbent assay at diagnosis, to be significantly higher in patients with CD who later developed strictures than in patients without strictures. The combination of concentrations of COL3A1 and anti-CSF2 might be used to identify pediatric patients at CD diagnosis who are at risk for future strictures. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00790543.
BACKGROUND & AIMS: There are few serum biomarkers to identify patients with Crohn's disease (CD) who are at risk for stricture development. The extracellular matrix components, collagen type III alpha 1 chain (COL3A1) and cartilage oligomeric matrix protein (COMP), could contribute to intestinal fibrosis. We investigated whether children with inflammatory CD (B1) who later develop strictures (B2) have increased plasma levels of COL3A1 or COMP at diagnosis, compared with children who remain B1. We compared results with previously studied biomarkers, including autoantibodies against colony-stimulating factor 2 (CSF2). METHODS: We selected 161 subjects (mean age, 12.2 y; 62% male) from the Risk Stratification and Identification of Immunogenic and Microbial Markers of Rapid Disease Progression in Children with Crohn's cohort, completed at 28 sites in the United States and Canada from 2008 through 2012. The children underwent colonoscopy and upper endoscopy at diagnosis and were followed up every 6 months for 36 months; plasma samples were collected at baseline. Based on CD phenotype, children were separated to group 1 (B1 phenotype at diagnosis and follow-up evaluation), group 2 (B2 phenotype at diagnosis), or group 3 (B1 phenotype at diagnosis who developed strictures during follow-up evaluation). Plasma samples were collected from patients and 40 children without inflammatory bowel disease (controls) at baseline and analyzed by enzyme-linked immunosorbent assay to measure COL3A1 and COMP. These results were compared with those from a previous biomarker study. The Kruskal-Wallis test and the pairwise Dunn test with Bonferroni correction were used to compare differences among groups. RESULTS: The median baseline concentration of COL3A1 was significantly higher in plasma from group 3 vs group 1 (P < .01) and controls (P = .01). Median baseline plasma concentrations of COMP did not differ significantly among groups. A model comprising baseline concentrations of COL3A1 and anti-CSF2 identified patients with B2 vs B1 CD with an area under the curve of 0.80 (95% CI, 0.71-0.89); the combined concentration identified patients with strictures with a sensitivity value of 0.70 (95% CI, 0.55-0.83) and a specificity value of 0.83 (95% CI, 0.67-0.93). CONCLUSIONS: We found median plasma concentrations of COL3A1, measured by enzyme-linked immunosorbent assay at diagnosis, to be significantly higher in patients with CD who later developed strictures than in patients without strictures. The combination of concentrations of COL3A1 and anti-CSF2 might be used to identify pediatric patients at CD diagnosis who are at risk for future strictures. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00790543.
Authors: Manuel Alvarez-Lobos; Juan I Arostegui; Miquel Sans; Dolors Tassies; Susana Plaza; Salvadora Delgado; Antonio M Lacy; Josep M Pique; Jordi Yagüe; Julián Panés Journal: Ann Surg Date: 2005-11 Impact factor: 12.969
Authors: Xiaonan Han; Kanji Uchida; Ingrid Jurickova; Diana Koch; Tara Willson; Charles Samson; Erin Bonkowski; Anna Trauernicht; Mi-Ok Kim; Gitit Tomer; Marla Dubinsky; Scott Plevy; Subra Kugathsan; Bruce C Trapnell; Lee A Denson Journal: Gastroenterology Date: 2008-12-24 Impact factor: 22.682
Authors: William M C Rosenberg; Michael Voelker; Robert Thiel; Michael Becka; Alastair Burt; Detlef Schuppan; Stefan Hubscher; Tania Roskams; Massimo Pinzani; Michael J P Arthur Journal: Gastroenterology Date: 2004-12 Impact factor: 22.682
Authors: Ingrid Jurickova; Erin Bonkowski; Elizabeth Angerman; Elizabeth Novak; Alex Huron; Grayce Akers; Kentaro Iwasawa; Tzipi Braun; Rotem Hadar; Maria Hooker; Sarah Han; David J Cutler; David T Okou; Subra Kugathasan; Anil Jegga; James Wells; Takanori Takebe; Kevin P Mollen; Yael Haberman; Lee A Denson Journal: Inflamm Bowel Dis Date: 2022-07-01 Impact factor: 7.290
Authors: Ilyssa O Gordon; Suha Abushamma; Jacob A Kurowski; Stefan D Holubar; Lei Kou; Ruishen Lyu; Florian Rieder Journal: J Crohns Colitis Date: 2022-06-24 Impact factor: 10.020
Authors: Calen A Steiner; Jeffrey A Berinstein; Jeremy Louissaint; Peter D R Higgins; Jason R Spence; Carol Shannon; Cathy Lu; Ryan W Stidham; Joel G Fletcher; David H Bruining; Brian G Feagan; Vipul Jairath; Mark E Baker; Dominik Bettenworth; Florian Rieder Journal: Clin Gastroenterol Hepatol Date: 2021-06-02 Impact factor: 11.382