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

Minar, Phillip MD1; Haberman, Yael MD, PhD1; Jurickova, Ingrid MD1; Wen, Ting PhD2; Rothenberg, Marc E. MD, PhD2; Kim, Mi-Ok PhD3; Saeed, Shehzad A. MD1; Baldassano, Robert N. MD4; Stephens, Michael MD5; Markowitz, James MD6; Rosh, Joel MD7; Crandall, Wallace V. MD8; Heyman, Melvin B. MD9; Mack, David R. MD10; Griffiths, Anne M. MD11; Baker, Susan S. MD, PhD12; Hyams, Jeffrey S. MD13; Kugathasan, Subra MD14; Denson, Lee A. MD1

doi: 10.1097/MIB.0000000000000049
Original Clinical Articles

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.

Article first published online 30 April 2014.

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.

Reprints: Phillip Minar, MD, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, MLC 2010, 3333 Burnet Avenue, Cincinnati, OH 45229 (e-mail: phillip.minar@cchmc.org).

Supported by National Institutes of Health (NIH) training grant T32 DK007727 (P.M.), NIH R01 DK078683 (L.A.D.), the Integrative Morphology and Flow Cytometry cores of the NIH-supported Cincinnati Children's Hospital Research Foundation Digestive Health Center (1P30DK078392-01), and the Crohn's and Colitis Foundation of America sponsored RISK study through PRO-KIIDS.

The authors have no conflicts of interest to disclose.

Received February 18, 2014

Accepted March 14, 2014

© Crohn's & Colitis Foundation of America, Inc.
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