Utility of neutrophil Fcγ receptor I (CD64) index as a biomarker for mucosal inflammation in pediatric Crohn's disease

Phillip Minar, Yael Haberman, Ingrid Jurickova, Ting Wen, Marc E. Rothenberg, Mi Ok Kim, Shehzad A. Saeed, Robert N. Baldassano, Michael Stephens, James Markowitz, Joel Rosh, Wallace V. Crandall, Melvin B. Heyman, David R. Mack, Anne M. Griffiths, Susan S. Baker, Jeffrey S. Hyams, Subra Kugathasan, Lee A. Denson

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1037-1048
Number of pages12
JournalInflammatory bowel diseases
Volume20
Issue number6
DOIs
StatePublished - Jan 1 2014

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Fc Receptors
Crohn Disease
Neutrophils
Biomarkers
Inflammation
Ileal Diseases
RNA Sequence Analysis
Recurrence
Inflammatory Bowel Diseases
Pediatric Crohn's disease
Biopsy
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Cite this

Minar, P., Haberman, Y., Jurickova, I., Wen, T., Rothenberg, M. E., Kim, M. O., ... 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. https://doi.org/10.1097/MIB.0000000000000049
Minar, Phillip ; Haberman, Yael ; Jurickova, Ingrid ; Wen, Ting ; Rothenberg, Marc E. ; Kim, Mi Ok ; Saeed, Shehzad A. ; Baldassano, Robert N. ; Stephens, Michael ; Markowitz, James ; Rosh, Joel ; Crandall, Wallace V. ; Heyman, Melvin B. ; Mack, David R. ; Griffiths, Anne M. ; Baker, Susan S. ; Hyams, Jeffrey S. ; Kugathasan, Subra ; Denson, Lee A. / Utility of neutrophil Fcγ receptor I (CD64) index as a biomarker for mucosal inflammation in pediatric Crohn's disease. In: Inflammatory bowel diseases. 2014 ; Vol. 20, No. 6. pp. 1037-1048.
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abstract = "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.",
author = "Phillip Minar and Yael Haberman and Ingrid Jurickova and Ting Wen and Rothenberg, {Marc E.} and Kim, {Mi Ok} and Saeed, {Shehzad A.} and Baldassano, {Robert N.} and Michael Stephens and James Markowitz and Joel Rosh and Crandall, {Wallace V.} and Heyman, {Melvin B.} and Mack, {David R.} and Griffiths, {Anne M.} and Baker, {Susan S.} and Hyams, {Jeffrey S.} and Subra Kugathasan and Denson, {Lee A.}",
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Minar, P, Haberman, Y, Jurickova, I, Wen, T, Rothenberg, ME, Kim, MO, Saeed, SA, Baldassano, RN, Stephens, M, Markowitz, J, Rosh, J, Crandall, WV, Heyman, MB, Mack, DR, Griffiths, AM, Baker, SS, Hyams, JS, Kugathasan, S & Denson, LA 2014, 'Utility of neutrophil Fcγ receptor I (CD64) index as a biomarker for mucosal inflammation in pediatric Crohn's disease', Inflammatory bowel diseases, vol. 20, no. 6, pp. 1037-1048. https://doi.org/10.1097/MIB.0000000000000049

Utility of neutrophil Fcγ receptor I (CD64) index as a biomarker for mucosal inflammation in pediatric Crohn's disease. / Minar, Phillip; Haberman, Yael; Jurickova, Ingrid; Wen, Ting; Rothenberg, Marc E.; Kim, Mi Ok; Saeed, Shehzad A.; Baldassano, Robert N.; Stephens, Michael; Markowitz, James; Rosh, Joel; Crandall, Wallace V.; Heyman, Melvin B.; Mack, David R.; Griffiths, Anne M.; Baker, Susan S.; Hyams, Jeffrey S.; Kugathasan, Subra; Denson, Lee A.

In: Inflammatory bowel diseases, Vol. 20, No. 6, 01.01.2014, p. 1037-1048.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Utility of neutrophil Fcγ receptor I (CD64) index as a biomarker for mucosal inflammation in pediatric Crohn's disease

AU - Minar, Phillip

AU - Haberman, Yael

AU - Jurickova, Ingrid

AU - Wen, Ting

AU - Rothenberg, Marc E.

AU - Kim, Mi Ok

AU - Saeed, Shehzad A.

AU - Baldassano, Robert N.

AU - Stephens, Michael

AU - Markowitz, James

AU - Rosh, Joel

AU - Crandall, Wallace V.

AU - Heyman, Melvin B.

AU - Mack, David R.

AU - Griffiths, Anne M.

AU - Baker, Susan S.

AU - Hyams, Jeffrey S.

AU - Kugathasan, Subra

AU - Denson, Lee A.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

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