Inflammatory Bowel Diseases

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Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0000000000000049
Original Clinical Articles

Utility of Neutrophil Fcγ 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

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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.

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

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