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. 2017 Dec 19;24(1):198-208.
doi: 10.1093/ibd/izx022.

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

Phillip Minar  1 , Kimberly Jackson  1 , Yi-Ting Tsai  1 , Heidi Sucharew  2 , Michael J Rosen  1 , Lee A Denson  2
Affiliations

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

Phillip Minar et al. Inflamm Bowel Dis. .

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 VSports手机版. .

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) V体育安卓版. .

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 V体育ios版. 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. VSports最新版本.

Keywords: CD64 biomarker; Crohn’s disease; pediatrics V体育平台登录. .

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Figures

FIGURE 1.
FIGURE 1.
Neutrophil CD64 index, fecal calprotectin, soluble CD64, and neutrophil CD64 activity index were measured prior to endoscopy. The result of each biomarker was tested for each diagnosis by the Kruskal-Wallis test, with Dunn’s test used for pairwise comparisons. *P < 0.05; **P < 0.01; ***P < 0.001.
FIGURE 2.
FIGURE 2.
Patients with suspected IBD were referred for colonoscopy, with blood and stool biomarkers obtained prior to the endoscopy. The performance (AUC) of each biomarker to distinguish Crohn’s from controls was calculated. We also tested for statistical significance between the AUC for each biomarker curve. (A) The AUC for neutrophil CD64 index + albumin combination (81% sensitive, 94% specific) was significantly better than neutrophil CD64 index alone (P = 0.03) while the combination of CD64 index + calprotectin (91% sensitive, 88% specific) was also superior to CD64 index alone (P = 0.02). (B) The AUC of sCD64 + albumin was similar to soluble CD64 alone while the combination of soluble CD64 + calprotectin (94% sensitive, 100% specific) was significantly higher than soluble CD64 alone (P = 0.02). *P < 0.05.
FIGURE 3.
FIGURE 3.
The CD64 biomarkers and fecal calprotectin were collected prior to endoscopy, with endoscopic severity determined by the Simple Endoscopic Score–Crohn’s Disease. (A) Neutrophil CD64 index, (B) fecal calprotectin, (C) soluble CD64, and (D) neutrophil CD64 activity ratio were evaluated across 4 levels of endoscopic severity by Kruskal-Wallis test with Dunn’s post-test for pairwise comparisons. *P < 0.05; **P < 0.01; ***P < 0.001.
FIGURE 4.
FIGURE 4.
Endoscopic active was defined by an SES-CD ≥3, with blood and stool biomarkers obtained prior to the endoscopy. The performance (AUC) of each biomarker to distinguish active Crohn’s from inactive Crohn’s was calculated. We also tested for statistical significance between the AUC for each biomarker curve. (A) The AUC for neutrophil CD64 index + albumin combination was not different than neutrophil CD64 index alone (P = 0.14) while combination CD64 index + calprotectin (89% sensitive, 88% specific) was superior to the neutrophil CD64 index alone (P = 0.02). (B) The AUC for soluble CD64 + albumin was not different than soluble CD64 alone (P = 0.42), while the combination of soluble CD64 + calprotectin (86% sensitive, 86% specific) was also not superior to soluble CD64 alone (P = 0.25).
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