AlphaE Integrin Expression Is Increased in the Ileum Relative to the Colon and Unaffected by Inflammation

Ryan Ichikawa, Christopher A. Lamb, Jeff Eastham-Anderson, Alexis Scherl, Laura E. H. Raffals, William Alvis Faubion, Miriam R. Bennett, Anna K. Long, John C. Mansfield, John A. Kirby, Mary E. Keir

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Recent findings suggest that αE expression is enriched on effector T cells and that intestinal αE+ T cells have increased expression of inflammatory cytokines. αE integrin expression is a potential predictive biomarker for response to etrolizumab, a monoclonal antibody against β7 integrin that targets both α4β7 and αEβ7. We evaluated the prevalence and localization of αE+ cells as well as total αE gene expression in healthy and inflammatory bowel disease patients. Methods: αE+ cells were identified in ileal and colonic biopsies by immunohistochemistry and counted using an automated algorithm. Gene expression was assessed by quantitative reverse-transcriptase polymerase chain reaction. Results: In both healthy and inflammatory bowel disease patients, significantly more αE+ cells were present in the epithelium and lamina propria of ileal compared with colonic biopsies. αE gene expression levels were also significantly higher in ileal compared with colonic biopsies. Paired biopsies from the same patient showed moderate correlation of αE expression between the ileum and colon. Inflammation did not affect αE expression, and neither endoscopy nor histology scores correlated with αE gene expression. αE expression was not different between patients based on concomitant medication use except 5-aminosalicylic acid. Conclusion: αE+ cells, which have been shown to have inflammatory potential, are increased in the ileum in comparison with the colon in both Crohn's disease and ulcerative colitis, as well as in healthy subjects. In inflammatory bowel disease patients, αE levels are stable, regardless of inflammatory status or most concomitant medications, which could support its use as a biomarker for etrolizumab.

Original languageEnglish (US)
Pages (from-to)1191-1199
Number of pages9
JournalJournal of Crohn's & colitis
Volume12
Issue number10
DOIs
StatePublished - Nov 9 2018

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Ileum
Colon
Inflammation
Inflammatory Bowel Diseases
Biopsy
Gene Expression
Integrins
Biomarkers
T-Lymphocytes
Mesalamine
Reverse Transcriptase Polymerase Chain Reaction
Ulcerative Colitis
Crohn Disease
Endoscopy
Histology
Healthy Volunteers
Mucous Membrane
Epithelium
Immunohistochemistry
Monoclonal Antibodies

ASJC Scopus subject areas

  • Gastroenterology

Cite this

AlphaE Integrin Expression Is Increased in the Ileum Relative to the Colon and Unaffected by Inflammation. / Ichikawa, Ryan; Lamb, Christopher A.; Eastham-Anderson, Jeff; Scherl, Alexis; Raffals, Laura E. H.; Faubion, William Alvis; Bennett, Miriam R.; Long, Anna K.; Mansfield, John C.; Kirby, John A.; Keir, Mary E.

In: Journal of Crohn's & colitis, Vol. 12, No. 10, 09.11.2018, p. 1191-1199.

Research output: Contribution to journalArticle

Ichikawa, R, Lamb, CA, Eastham-Anderson, J, Scherl, A, Raffals, LEH, Faubion, WA, Bennett, MR, Long, AK, Mansfield, JC, Kirby, JA & Keir, ME 2018, 'AlphaE Integrin Expression Is Increased in the Ileum Relative to the Colon and Unaffected by Inflammation', Journal of Crohn's & colitis, vol. 12, no. 10, pp. 1191-1199. https://doi.org/10.1093/ecco-jcc/jjy084
Ichikawa, Ryan ; Lamb, Christopher A. ; Eastham-Anderson, Jeff ; Scherl, Alexis ; Raffals, Laura E. H. ; Faubion, William Alvis ; Bennett, Miriam R. ; Long, Anna K. ; Mansfield, John C. ; Kirby, John A. ; Keir, Mary E. / AlphaE Integrin Expression Is Increased in the Ileum Relative to the Colon and Unaffected by Inflammation. In: Journal of Crohn's & colitis. 2018 ; Vol. 12, No. 10. pp. 1191-1199.
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AU - Ichikawa, Ryan

AU - Lamb, Christopher A.

AU - Eastham-Anderson, Jeff

AU - Scherl, Alexis

AU - Raffals, Laura E. H.

AU - Faubion, William Alvis

AU - Bennett, Miriam R.

AU - Long, Anna K.

AU - Mansfield, John C.

AU - Kirby, John A.

AU - Keir, Mary E.

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N2 - Background: Recent findings suggest that αE expression is enriched on effector T cells and that intestinal αE+ T cells have increased expression of inflammatory cytokines. αE integrin expression is a potential predictive biomarker for response to etrolizumab, a monoclonal antibody against β7 integrin that targets both α4β7 and αEβ7. We evaluated the prevalence and localization of αE+ cells as well as total αE gene expression in healthy and inflammatory bowel disease patients. Methods: αE+ cells were identified in ileal and colonic biopsies by immunohistochemistry and counted using an automated algorithm. Gene expression was assessed by quantitative reverse-transcriptase polymerase chain reaction. Results: In both healthy and inflammatory bowel disease patients, significantly more αE+ cells were present in the epithelium and lamina propria of ileal compared with colonic biopsies. αE gene expression levels were also significantly higher in ileal compared with colonic biopsies. Paired biopsies from the same patient showed moderate correlation of αE expression between the ileum and colon. Inflammation did not affect αE expression, and neither endoscopy nor histology scores correlated with αE gene expression. αE expression was not different between patients based on concomitant medication use except 5-aminosalicylic acid. Conclusion: αE+ cells, which have been shown to have inflammatory potential, are increased in the ileum in comparison with the colon in both Crohn's disease and ulcerative colitis, as well as in healthy subjects. In inflammatory bowel disease patients, αE levels are stable, regardless of inflammatory status or most concomitant medications, which could support its use as a biomarker for etrolizumab.

AB - Background: Recent findings suggest that αE expression is enriched on effector T cells and that intestinal αE+ T cells have increased expression of inflammatory cytokines. αE integrin expression is a potential predictive biomarker for response to etrolizumab, a monoclonal antibody against β7 integrin that targets both α4β7 and αEβ7. We evaluated the prevalence and localization of αE+ cells as well as total αE gene expression in healthy and inflammatory bowel disease patients. Methods: αE+ cells were identified in ileal and colonic biopsies by immunohistochemistry and counted using an automated algorithm. Gene expression was assessed by quantitative reverse-transcriptase polymerase chain reaction. Results: In both healthy and inflammatory bowel disease patients, significantly more αE+ cells were present in the epithelium and lamina propria of ileal compared with colonic biopsies. αE gene expression levels were also significantly higher in ileal compared with colonic biopsies. Paired biopsies from the same patient showed moderate correlation of αE expression between the ileum and colon. Inflammation did not affect αE expression, and neither endoscopy nor histology scores correlated with αE gene expression. αE expression was not different between patients based on concomitant medication use except 5-aminosalicylic acid. Conclusion: αE+ cells, which have been shown to have inflammatory potential, are increased in the ileum in comparison with the colon in both Crohn's disease and ulcerative colitis, as well as in healthy subjects. In inflammatory bowel disease patients, αE levels are stable, regardless of inflammatory status or most concomitant medications, which could support its use as a biomarker for etrolizumab.

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