Utility of Neutrophil Fcγ Receptor I (CD64) Index as a Biomarker for Mucosal Inflammation in Pediatric Crohn's Disease
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).
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.
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 index1.0 (P < 0.01).
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.
Rothenberg, M. E.,
Saeed, S. A.,
Baldassano, R. N.,
Crandall, W. V.,
Heyman, M. B.,
Mack, D. R.,
Griffiths, A. M.,
Baker, S. S.,
Hymans, J. S.,
& Denson, L. A.
(2014). Utility of Neutrophil Fcγ Receptor I (CD64) Index as a Biomarker for Mucosal Inflammation in Pediatric Crohn's Disease. Inflammatory Bowel Diseases, 20 (6), 1037-1048.