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

• Type of Material: Article
• 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
• Language: English
• Date: 2014-06-01
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option B - CC-BY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Copyright © 2014 Crohn's & Colitis Foundation of America, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1097/MIB.0000000000000049
• Title of Journal or Parent Work: Inflammatory Bowel Diseases
• ISSN: 1078-0998
• Volume: 20
• Issue: 6
• Start Page: 1037
• End Page: 1048
• Grant/Funding Information: This work was supported by NIH training grant T32 DK007727 (PM); NIH R01 DK078683 (LAD); the Integrative Morphology and Flow Cytometry cores of the National Institutes of Health (NIH)-supported Cincinnati Children's Hospital Research Foundation Digestive Health Center (1P30DK078392-01); and the Crohn's & Colitis Foundation of America sponsored RISK study through PRO-KIIDS.
• Keywords: SES-CD; CD64 index; INFLIXIMAB; Gastroenterology & Hepatology; Life Sciences & Biomedicine; biomarker; CLINICAL REMISSION; QUALITY IMPROVEMENT; innate immune system in IBD; pediatric Crohn's disease; Science & Technology; DIAGNOSTIC MARKER; Fc gamma receptor; FECAL CALPROTECTIN; IRRITABLE-BOWEL-SYNDROME; EXPRESSION; BLOOD LEUKOCYTES; VALIDATION
• Research Categories: Health Sciences, Pathology; Health Sciences, Medicine and Surgery; Health Sciences, Immunology

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.