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

Background:Neutrophil expression of the Fc&ggr; 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 Fc&ggr;RI/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 Fc&ggr;RIA 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.

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