Abstract
Background: Up to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. The aim of this study was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. Methods: An observational, longitudinal, prospective cohort study was conducted. The study population comprised 38 patients with IBD aged < 18 years who started treatment with infliximab or adalimumab (29 responders and nine non-responders). Whole gene expression profiles from total RNA isolated from whole blood samples of six responders and six non-responders taken before administration of the biologic and after two weeks of therapy were analyzed using next-generation RNA sequencing. The expression of six selected genes was measured for purposes of validation in all of the 38 patients recruited using qPCR. Results: Genes were differentially expressed in non-responders and responders (32 before initiation of treatment and 44 after two weeks, Log2FC (Fold change) >0.6 or <−0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B, and GBP1 were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, p value < 0.05). Conclusion: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.
Highlights
Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn disease (CD), is a multifactorial autoimmune disorder in which a quarter of patients are diagnosed when aged under 18 years [1,2]
As there are no gene expression changes with an associated Benjamini and Hochberg-adjusted p value < 0.05, we considered candidates to be confirmed as such by qPCR genes with |log2FC| > 0.6 and a non-adjusted p value < 0.05
Finding specific biomarkers for children is necessary since genetics has a more important role in pediatric IBD (pIBD) than in adult disease
Summary
Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn disease (CD), is a multifactorial autoimmune disorder in which a quarter of patients are diagnosed when aged under 18 years [1,2]. The use of biological therapy, such as anti-Tumor Necrosis Factor (anti-TNF) agents, has dramatically changed the treatment of autoimmune disease, including IBD. The use of these drugs is often linked to more severe symptoms of pIBD [4]. Up to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. FCGR1A, FCGR1B, and GBP1 were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, p value < 0.05). Conclusion: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD
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