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Anti-TNF-α Biologics Do Not Reverse CDX2 Downregulation in Patients with Crohn's Disease

Mamoun Younes1, Erik Rahimi2, Andrew W DuPont2

  • 1Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, and Memorial-Hermann Hospital-TMC, Houston, TX, USA Mamoun.Younes@uth.tmc.edu.

Annals of Clinical and Laboratory Science
|May 6, 2020
PubMed
Abstract

Insights

Crohn's disease (CD) is associated with reduced caudal-related homeobox transcription factor 2 (CDX2) expression. Anti-tumor necrosis factor-alpha (TNF-α) biologics did not restore normal CDX2 levels in CD patients.

Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Immunology

Background:

  • Caudal-related homeobox transcription factor 2 (CDX2) is crucial for intestinal epithelial cell functions.
  • Tumor necrosis factor-alpha (TNF-α) downregulates CDX2 expression in vitro.
  • Infliximab, an anti-TNF-α drug, mitigates TNF-α-induced CDX2 reduction in cell cultures.

Purpose of the Study:

  • To investigate CDX2 expression levels in Crohn's disease (CD) patient biopsies.
  • To determine if anti-TNF-α biologic therapy reverses CDX2 downregulation in CD patients.

Main Methods:

  • Ileocolonic biopsies from CD patients, CD patients on anti-TNF-α therapy (CD-T), and controls were analyzed.
  • Immunohistochemical staining for CDX2 was performed.
  • Quantitative analysis of CDX2 expression was conducted using OTMIAS digital image analysis.

Main Results:

  • CDX2 expression was significantly lower in both CD and CD-T groups compared to controls (p=0.0003).
  • Anti-TNF-α treatment (CD-T) did not lead to a significant increase in CDX2 expression (p=0.3292).
  • CDX2 levels in CD-T patients remained significantly lower than in controls (p=0.0002).

Conclusions:

  • CDX2 is downregulated in the context of Crohn's disease.
  • Anti-TNF-α biologic therapy does not restore normal CDX2 expression levels in CD patients.

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