Utility of neutrophil Fcγ receptor I (CD64) index as a biomarker for mucosal inflammation in pediatric Crohn's disease.
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.
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.
Phillip
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Minar
Yael
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Haberman
Ingrid
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Jurickova
Ting
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Wen
Marc E
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Rothenberg
Mi-Ok
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Kim
Shehzad A
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Saeed
Robert N
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Baldassano
Michael
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Stephens
James
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Markowitz
Joel
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Rosh
Wallace V
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Crandall
Melvin B
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Heyman
David R
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Mack
Anne M
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Griffiths
Susan S
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Baker
Jeffrey S
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Hyams
Subra
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Kugathasan
Lee A
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Denson
D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003424:Crohn Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D005260:Female; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D012007:Rectum / Q000276:immunology / Q000378:metabolism; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D012680:Sensitivity and Specificity
D015415:Biomarkers; D040502:Calgranulin B; C489017:FCGR1A protein, human; D017452:Receptors, IgG