Evaluation of optimal biopsy location for assessment of histological activity, transcriptomic and immunohistochemical analyses in patients with active Crohn’s disease

Gregor Novak, Toer Stevens, Tanja Van Viegen, Peter Bossuyt, Borut Štabuc, Jenny Jeyarajah, Guangyong Zou, Ingrid C. Gaemers, Trevor D. McKee, Fred Fu, Lisa M. Shackelton, Reena Khanna, Gijs R. van den Brink, William J. Sandborn, Brian G. Feagan, Rish Pai, Vipul Jairath, Niels Vande Casteele, Geert D’Haens

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown. Aim: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells. Methods: Fifty-one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer. Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins-6, -8 and -23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase-positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient. Results: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase-positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. Conclusions: Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures.

Original languageEnglish (US)
Pages (from-to)1401-1409
Number of pages9
JournalAlimentary Pharmacology and Therapeutics
Volume49
Issue number11
DOIs
StatePublished - Jun 1 2019

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Crohn Disease
Ulcer
Biopsy
Ileum
Colon
Peroxidase
RNA
Gene Expression
Interleukin-8
Interleukin-6
Immunohistochemistry
Polymerase Chain Reaction
Research

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

Cite this

Evaluation of optimal biopsy location for assessment of histological activity, transcriptomic and immunohistochemical analyses in patients with active Crohn’s disease. / Novak, Gregor; Stevens, Toer; Van Viegen, Tanja; Bossuyt, Peter; Štabuc, Borut; Jeyarajah, Jenny; Zou, Guangyong; Gaemers, Ingrid C.; McKee, Trevor D.; Fu, Fred; Shackelton, Lisa M.; Khanna, Reena; van den Brink, Gijs R.; Sandborn, William J.; Feagan, Brian G.; Pai, Rish; Jairath, Vipul; Vande Casteele, Niels; D’Haens, Geert.

In: Alimentary Pharmacology and Therapeutics, Vol. 49, No. 11, 01.06.2019, p. 1401-1409.

Research output: Contribution to journalArticle

Novak, G, Stevens, T, Van Viegen, T, Bossuyt, P, Štabuc, B, Jeyarajah, J, Zou, G, Gaemers, IC, McKee, TD, Fu, F, Shackelton, LM, Khanna, R, van den Brink, GR, Sandborn, WJ, Feagan, BG, Pai, R, Jairath, V, Vande Casteele, N & D’Haens, G 2019, 'Evaluation of optimal biopsy location for assessment of histological activity, transcriptomic and immunohistochemical analyses in patients with active Crohn’s disease', Alimentary Pharmacology and Therapeutics, vol. 49, no. 11, pp. 1401-1409. https://doi.org/10.1111/apt.15250
Novak, Gregor ; Stevens, Toer ; Van Viegen, Tanja ; Bossuyt, Peter ; Štabuc, Borut ; Jeyarajah, Jenny ; Zou, Guangyong ; Gaemers, Ingrid C. ; McKee, Trevor D. ; Fu, Fred ; Shackelton, Lisa M. ; Khanna, Reena ; van den Brink, Gijs R. ; Sandborn, William J. ; Feagan, Brian G. ; Pai, Rish ; Jairath, Vipul ; Vande Casteele, Niels ; D’Haens, Geert. / Evaluation of optimal biopsy location for assessment of histological activity, transcriptomic and immunohistochemical analyses in patients with active Crohn’s disease. In: Alimentary Pharmacology and Therapeutics. 2019 ; Vol. 49, No. 11. pp. 1401-1409.
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abstract = "Background: The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown. Aim: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells. Methods: Fifty-one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer. Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins-6, -8 and -23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase-positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient. Results: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase-positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. Conclusions: Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures.",
author = "Gregor Novak and Toer Stevens and {Van Viegen}, Tanja and Peter Bossuyt and Borut Štabuc and Jenny Jeyarajah and Guangyong Zou and Gaemers, {Ingrid C.} and McKee, {Trevor D.} and Fred Fu and Shackelton, {Lisa M.} and Reena Khanna and {van den Brink}, {Gijs R.} and Sandborn, {William J.} and Feagan, {Brian G.} and Rish Pai and Vipul Jairath and {Vande Casteele}, Niels and Geert D’Haens",
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T1 - Evaluation of optimal biopsy location for assessment of histological activity, transcriptomic and immunohistochemical analyses in patients with active Crohn’s disease

AU - Novak, Gregor

AU - Stevens, Toer

AU - Van Viegen, Tanja

AU - Bossuyt, Peter

AU - Štabuc, Borut

AU - Jeyarajah, Jenny

AU - Zou, Guangyong

AU - Gaemers, Ingrid C.

AU - McKee, Trevor D.

AU - Fu, Fred

AU - Shackelton, Lisa M.

AU - Khanna, Reena

AU - van den Brink, Gijs R.

AU - Sandborn, William J.

AU - Feagan, Brian G.

AU - Pai, Rish

AU - Jairath, Vipul

AU - Vande Casteele, Niels

AU - D’Haens, Geert

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Background: The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown. Aim: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells. Methods: Fifty-one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer. Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins-6, -8 and -23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase-positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient. Results: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase-positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. Conclusions: Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures.

AB - Background: The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown. Aim: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells. Methods: Fifty-one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer. Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins-6, -8 and -23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase-positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient. Results: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase-positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. Conclusions: Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures.

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