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Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease

Sara Salvador-Martín1, Bartosz Kaczmarczyk1, Rebeca Álvarez2

  • 1Pharmacy Department, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.

Pharmaceutics
|January 12, 2021
PubMed

Insights

Pharmacogenomic markers FCGR1A, FCGR1B, and GBP1 predict early response to anti-tumor necrosis factor (anti-TNF) therapy in pediatric inflammatory bowel disease (IBD) patients. This finding aids in tailoring treatment for non-responders.

Area of Science:

  • Pharmacogenomics
  • Molecular Biology
  • Pediatric Gastroenterology

Background:

  • Up to 30% of pediatric inflammatory bowel disease (IBD) patients exhibit primary non-response to anti-tumor necrosis factor (anti-TNF) therapies.
  • Identifying biomarkers for early treatment response is crucial for optimizing therapeutic strategies in pediatric IBD.
  • Current treatment selection for pediatric IBD lacks predictive pharmacogenomic guidance.

Purpose of the Study:

  • To identify pharmacogenomic markers that predict early response to anti-TNF therapy in pediatric IBD patients.
  • To investigate gene expression profiles associated with treatment response in pediatric IBD.
  • To establish predictive biomarkers for infliximab or adalimumab efficacy.

Main Methods:

  • Observational, longitudinal, prospective cohort study of 38 pediatric IBD patients (<18 years).
  • Whole gene expression profiling using next-generation RNA sequencing on blood samples from responders and non-responders before and after two weeks of anti-TNF therapy.
  • Quantitative real-time PCR (qPCR) validation of selected gene expression in all 38 patients.

Main Results:

  • Differential gene expression observed between responders and non-responders (32 genes pre-treatment, 44 genes post-treatment).
  • FCGR1A, FCGR1B, and GBP1 genes were significantly overexpressed in non-responders two weeks post-anti-TNF initiation (Log2FC > 1.0, p < 0.05).
  • Validated overexpression of FCGR1A, FCGR1B, and GBP1 in non-responders confirmed their potential as predictive biomarkers.

Conclusions:

  • FCGR1A, FCGR1B, and GBP1 gene expression serve as pharmacogenomic biomarkers for predicting early response to anti-TNF agents in pediatric IBD.
  • These biomarkers may help identify non-responders early, allowing for timely treatment adjustments.
  • This research contributes to personalized medicine approaches in managing pediatric IBD.
Abstract

Keywords:
Crohn diseaseadalimumabbiomarkergene expressioninflammatory bowel diseaseinfliximabulcerative colitis

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