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

2021; Multidisciplinary Digital Publishing Institute; Volume: 13; Issue: 1 Linguagem: Inglês

10.3390/pharmaceutics13010077

1999-4923

Sara Salvador‐Martín, B. Kaczmarczyk, Rebeca Álvarez, Víctor Manuel Navas‐López, Carmen Gallego‐Fernández, Ana Moreno‐Álvarez, Alfonso Solar‐Boga, César Sánchez, María del Mar Tolín Hernani, Marta Velasco Rodríguez‐Belvís, Rosana Muñoz‐Codoceo, Alejandro Rodríguez Martínez, Concepción Álvarez del Vayo Benito, Ferrán Bossacoma, Gemma Pujol‐Muncunill, María J. Fobelo, Antonio Millán‐Jiménez, Lorena Magallares, Eva Martínez‐Ojinaga, Inés Loverdos, Francisco Javier Eizaguirre, José A. Blanca‐García, Susana Clemente, Ruth García‐Romero, Vicente Merino‐Bohórquez, Rafael González de Caldas, Enrique Vázquez, Ana Dopazo, María Sanjurjo‐Sáez, Luis A. López‐Fernández,

Viral gastroenteritis research and epidemiology

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.