Utility of Neutrophil Fc gamma Receptor I (CD64) Index as a Biomarker for Mucosal Inflammation in Pediatric Crohn's Disease

• Authors: Phillip Minar, Cincinnati Children's Hospital Medical Center; Yael Haberman, Cincinnati Children's Hospital Medical Center; Ingrid Jurickova, Cincinnati Children's Hospital Medical Center; Ting Wen, Cincinnati Children's Hospital Medical Center; Marc E. Rothenberg, Cincinnati Children's Hospital Medical Center; Mi-Ok Kim, Cincinnati Children's Hospital Medical Center; Shehzad A. Saeed, Cincinnati Children's Hospital Medical Center; Robert N. Baldassano, University of Pennsylvania; Michael Stephens, Mayo Clinic; James Markowitz, Cohen Children's Medical Center of New York; Joel Rosh, Goryeb Children's Hospital/Atlantic Health; Wallace V. Crandall, Nationwide Children's Hospital; Melvin B. Heyman, University of California, San Francisco; David R. Mack, Children's Hospital of Eastern Ontario; Anne M. Griffiths, University of Toronto; Susan S. Baker, University at Buffalo; Jeffrey S. Hyams, Connecticut Children's Medical Center; Subramaniam Kugathasan, Emory University; Lee A. Denson, Cincinnati Children's Hospital Medical Center
• Journal Title: Inflammatory Bowel Diseases
• Volume: Volume 20, Number 6
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option B - CC-BY | 2014-06-01, Pages 1037-1048
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1097/MIB.0000000000000049
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, Immunology; Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Gastroenterology & Hepatology; innate immune system in IBD; Fc gamma receptor; CD64 index; pediatric Crohn's disease; biomarker; IRRITABLE-BOWEL-SYNDROME; FECAL CALPROTECTIN; QUALITY IMPROVEMENT; CLINICAL REMISSION; DIAGNOSTIC MARKER; BLOOD LEUKOCYTES; SES-CD; EXPRESSION; INFLIXIMAB; VALIDATION

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.