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oai:repisalud.isciii.es:20.500.12105/258972025-12-18T12:53:26Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Salvador-Martín, Sara author Rubbini, Gianluca author Vellosillo, Perceval author Zapata-Cobo, Paula author Velasco, Marta author Palomino, Laura M author Clemente, Susana author Segarra, Oscar author Moreno-Álvarez, Ana author Fernández-Lorenzo, Ana author Pérez-Moneo, Begoña author Montraveta, Montserrat author Sánchez, Cesar author Tolín, Mar author Loverdos, Inés author Fobelo, María José author Navas-López, Victor Manuel author Magallares, Lorena author García-Romero, Ruth author Torres-Peral, Ricardo author Rodríguez, Alejandro author Bossacoma, Ferrán author Merino-Bohórquez, Vicente author Salcedo, Enrique author Álvarez, Rebeca author Dopazo, Ana author Sanjurjo-Sáez, María author López-Fernández, Luis A author 2024-04 Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment. We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs. Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR = 2.3 ×10-7) as the most significant biological processes, and hemoglobin binding (FDR = 0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR = 0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3). We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs. Biomed Pharmacother. 2024 Apr:173:116299. Biomedicine & Pharmacotherapy 38401525 https://hdl.handle.net/20.500.12105/25897 Anti-TNF drugs Inflammatory bowel disease Pediatrics Pharmacogenomics RNA-seq Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment.