Validation of Neutrophil CD64 Blood Biomarkers to Detect Mucosal Inflammation in Pediatric Crohn's Disease.

Abstract

Background:

In a pilot study, neutrophil CD64 surface expression was significantly elevated in newly diagnosed, pediatric-onset Crohn's disease. We aimed to test the CD64 biomarkers (neutrophil CD64 surface expression and soluble CD64) as determinates for mucosal inflammation in a larger pediatric Crohn's cohort with the hypotheses that the CD64 biomarkers would reliably detect intestinal inflammation and correlate with endoscopic severity scores.

Methods:

We enrolled patients referred for colonoscopy for either suspected inflammatory bowel disease or with established Crohn's. Neutrophil CD64 index was determined by flow cytometry using a commercial kit (Leuko64, Trillium) and soluble CD64 by ELISA (LifeSpan).

Results:

A total of 209 patients (72 controls, 76 new inflammatory bowel disease patients, and 61 established Crohn's) were enrolled. Both neutrophil CD64 index and soluble CD64 were significantly elevated in new Crohn's compared with controls. The area under the curve (AUC) for neutrophil CD64 index ≥1 was 0.85 (95% confidence interval, 0.77-0.92), 75% sensitive and 89% specific for new Crohn's. Comparatively, soluble CD64 ≥39 ng/mL was 92% sensitive and 85% specific (AUC, 0.93) for new Crohn's. Neutrophil CD64 index, soluble CD64, and fecal calprotectin discriminated endoscopic inactive from moderate and severe activity while soluble CD64 differentiated endoscopic mild from moderate and severe activity. Neutrophil CD64 index (r = 0.46, P < 0.001) and fecal calprotectin (r = 0.55, P < 0.001) correlated well with the Simple Endoscopic Score-Crohn's disease. Spearman correlation between the CD64 index and calprotectin was 0.39 (P < 0.001).

Conclusions:

In a large Crohn's disease cohort, we found that neutrophil CD64 index and soluble CD64 were significantly elevated during active gastrointestinal inflammation.

• Authors: Phillip Minar, Kimberly Jackson, Yi-Ting Tsai, Heidi Sucharew, Michael J Rosen, Lee A Denson
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 24 Issue 1 Pg. 198-208 (12 19 2017) ISSN: 1536-4844 [Electronic] England
• PMID: 29272485 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: © 2017 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]

Chemical References

• Biomarkers
• Receptors, IgG

Topics

• Adolescent
• Adult
• Biomarkers (blood)
• Case-Control Studies
• Child
• Child, Preschool
• Cohort Studies
• Crohn Disease (complications)
• Female
• Humans
• Inflammation (blood, diagnosis, etiology)
• Intestinal Mucosa (metabolism, pathology)
• Male
• Neutrophils (metabolism)
• Pilot Projects
• Receptors, IgG (blood)
• Severity of Illness Index
• Young Adult