Phillip Minar1, Yael Haberman, Ingrid Jurickova, Ting Wen, Marc E Rothenberg, Mi-Ok Kim, Shehzad A Saeed, Robert N Baldassano, Michael Stephens, James Markowitz, Joel Rosh, Wallace V Crandall, Melvin B Heyman, David R Mack, Anne M Griffiths, Susan S Baker, Jeffrey S Hyams, Subra Kugathasan, Lee A Denson. 1. 1Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Divisions of 2Allergy and Immunology and 3Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; 4Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; 5Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; 6Division of Pediatric Gastroenterology and Nutrition, Cohen Children's Medical Center of New York, New Hyde Park, New York; 7Department of Pediatric Gastroenterology and Nutrition, Goryeb Children's Hospital/Atlantic Health System, Morristown, New Jersey; 8Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital, Columbus, Ohio; 9Department of Pediatrics, University of California, San Francisco, San Francisco, California; 10Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; 11Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; 12Digestive Diseases and Nutrition Center, Department of Pediatrics, University at Buffalo, Buffalo, New York; 13Division of Digestive Diseases and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut; and 14Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University, Atlanta, Georgia.
Abstract
BACKGROUND: Neutrophil expression of the Fcγ receptor I (CD64) is upregulated in adult patients with clinically active inflammatory bowel disease (IBD). We tested the relationship of CD64 with mucosal inflammation and clinical relapse in pediatric Crohn's disease (CD). METHODS: In a cohort of 208 newly diagnosed CD and 43 non-IBD controls, ileal expression of FcγRI/S100A9 was determined by RNA sequencing from biopsies obtained at ileocolonoscopy. In a second cohort, we tested for the peripheral blood polymorphonuclear neutrophil (PMN) CD64 index from 26 newly diagnosed CD, 30 non-IBD controls, and 83 children with established CD. RESULTS: Ileal FcγRIA mRNA expression was significantly elevated in CD at diagnosis compared with non-IBD controls (P < 0.001), and correlated with ileal S100A9 (calprotectin) expression (r = 0.83, P < 0.001). The median (range) PMN CD64 index for newly diagnosed CD was 2.3 (0.74-9.3) compared with 0.76 (0.39-1.2) for non-IBD controls (P < 0.001) with 96% sensitivity and 90% specificity at the cut point of 1.0. The PMN CD64 index significantly correlated with mucosal injury as measured by the simple endoscopic score for CD (r = 0.62, P < 0.001). Patients with CD in clinical remission receiving maintenance therapy with a PMN CD64 index <1.0 had a sustained remission rate of 95% over the following 12 months compared with 56% in those with a PMN CD64 index >1.0 (P < 0.01). CONCLUSIONS: An elevated PMN CD64 index is associated with both mucosal inflammation and an increased risk for clinical relapse in pediatric CD. The PMN CD64 index is a reliable marker for sustained remission in patients with CD receiving maintenance therapy.
BACKGROUND: Neutrophil expression of the Fcγ receptor I (CD64) is upregulated in adult patients with clinically active inflammatory bowel disease (IBD). We tested the relationship of CD64 with mucosal inflammation and clinical relapse in pediatric Crohn's disease (CD). METHODS: In a cohort of 208 newly diagnosed CD and 43 non-IBD controls, ileal expression of FcγRI/S100A9 was determined by RNA sequencing from biopsies obtained at ileocolonoscopy. In a second cohort, we tested for the peripheral blood polymorphonuclear neutrophil (PMN) CD64 index from 26 newly diagnosed CD, 30 non-IBD controls, and 83 children with established CD. RESULTS: Ileal FcγRIA mRNA expression was significantly elevated in CD at diagnosis compared with non-IBD controls (P < 0.001), and correlated with ileal S100A9 (calprotectin) expression (r = 0.83, P < 0.001). The median (range) PMN CD64 index for newly diagnosed CD was 2.3 (0.74-9.3) compared with 0.76 (0.39-1.2) for non-IBD controls (P < 0.001) with 96% sensitivity and 90% specificity at the cut point of 1.0. The PMN CD64 index significantly correlated with mucosal injury as measured by the simple endoscopic score for CD (r = 0.62, P < 0.001). Patients with CD in clinical remission receiving maintenance therapy with a PMN CD64 index <1.0 had a sustained remission rate of 95% over the following 12 months compared with 56% in those with a PMN CD64 index >1.0 (P < 0.01). CONCLUSIONS: An elevated PMN CD64 index is associated with both mucosal inflammation and an increased risk for clinical relapse in pediatric CD. The PMN CD64 index is a reliable marker for sustained remission in patients with CD receiving maintenance therapy.
Authors: G D'haens; S Van Deventer; R Van Hogezand; D Chalmers; C Kothe; F Baert; T Braakman; T Schaible; K Geboes; P Rutgeerts Journal: Gastroenterology Date: 1999-05 Impact factor: 22.682
Authors: Paul Rutgeerts; William J Sandborn; Brian G Feagan; Walter Reinisch; Allan Olson; Jewel Johanns; Suzanne Travers; Daniel Rachmilewitz; Stephen B Hanauer; Gary R Lichtenstein; Willem J S de Villiers; Daniel Present; Bruce E Sands; Jean Frédéric Colombel Journal: N Engl J Med Date: 2005-12-08 Impact factor: 91.245
Authors: J Kristinsson; A Røseth; M K Fagerhol; E Aadland; H Schjønsby; O P Børmer; N Raknerud; K Nygaard Journal: Dis Colon Rectum Date: 1998-03 Impact factor: 4.585
Authors: J M Kerst; M de Haas; C E van der Schoot; I C Slaper-Cortenbach; M Kleijer; A E von dem Borne; R H van Oers Journal: Blood Date: 1993-12-01 Impact factor: 22.113
Authors: Phillip Minar; Kimberly Jackson; Yi-Ting Tsai; Michael J Rosen; Michael Northcutt; Marat Khodoun; Fred D Finkelman; Lee A Denson Journal: Inflamm Bowel Dis Date: 2016-11 Impact factor: 5.325
Authors: Yael Haberman; Marina BenShoshan; Ayelet Di Segni; Phillip J Dexheimer; Tzipi Braun; Batia Weiss; Thomas D Walters; Robert N Baldassano; Joshua D Noe; James Markowitz; Joel Rosh; Melvin B Heyman; Anne M Griffiths; Wallace V Crandall; David R Mack; Susan S Baker; Richard Kellermayer; Ashish Patel; Anthony Otley; Steven J Steiner; Ajay S Gulati; Stephen L Guthery; Neal LeLeiko; Dedrick Moulton; Barbara S Kirschner; Scott Snapper; Camila Avivi; Iris Barshack; Maria Oliva-Hemker; Stanley A Cohen; David J Keljo; David Ziring; Yair Anikster; Bruce Aronow; Jeffrey S Hyams; Subra Kugathasan; Lee A Denson Journal: Inflamm Bowel Dis Date: 2018-01-18 Impact factor: 5.325
Authors: A Therrien; L Chapuy; M Bsat; M Rubio; G Bernard; E Arslanian; K Orlicka; A Weber; B-P Panzini; J Dorais; E-J Bernard; G Soucy; M Bouin; M Sarfati Journal: Clin Exp Immunol Date: 2018-11-28 Impact factor: 4.330
Authors: Ruben J Colman; Yi-Ting Tsai; Kimberly Jackson; Brendan M Boyle; Joshua D Noe; Jeffrey S Hyams; Geert R A M D'Haens; Johan van Limbergen; Michael J Rosen; Lee A Denson; Phillip Minar Journal: Inflamm Bowel Dis Date: 2021-06-15 Impact factor: 7.290
Authors: Jerzy Ostrowski; Michalina Dabrowska; Izabella Lazowska; Agnieszka Paziewska; Aneta Balabas; Anna Kluska; Maria Kulecka; Jakub Karczmarski; Filip Ambrozkiewicz; Magdalena Piatkowska; Krzysztof Goryca; Natalia Zeber-Lubecka; Jaroslaw Kierkus; Piotr Socha; Michal Lodyga; Maria Klopocka; Barbara Iwanczak; Katarzyna Bak-Drabik; Jaroslaw Walkowiak; Piotr Radwan; Urszula Grzybowska-Chlebowczyk; Bartosz Korczowski; Teresa Starzynska; Michal Mikula Journal: J Crohns Colitis Date: 2019-04-26 Impact factor: 9.071