PMID- 37383609 OWN - NLM STAT- MEDLINE DCOM- 20230703 LR - 20230703 IS - 2314-7156 (Electronic) IS - 2314-8861 (Print) IS - 2314-7156 (Linking) VI - 2023 DP - 2023 TI - Serum TGF-beta1 and CD14 Predicts Response to Anti-TNF-alpha Therapy in IBD. PG - 1535484 LID - 10.1155/2023/1535484 [doi] LID - 1535484 AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) agonists revolutionized therapeutic algorithms in inflammatory bowel disease (IBD) management. However, approximately every third IBD patient does not respond to this therapy in the long term, which delays efficient control of the intestinal inflammation. METHODS: We analyzed the power of serum biomarkers to predict the failure of anti-TNF-alpha. We collected serum of 38 IBD patients at therapy prescription and 38 weeks later and analyzed them with relation to therapy response (no-, partial-, and full response). We used enzyme-linked immunosorbent assay to quantify 16 biomarkers related to gut barrier (intestinal fatty acid-binding protein, liver fatty acid-binding protein, trefoil factor 3, and interleukin (IL)-33), microbial translocation, immune system regulation (TNF-alpha, CD14, lipopolysaccharide-binding protein, mannan-binding lectin, IL-18, transforming growth factor-beta1 (TGF-beta1), osteoprotegerin (OPG), insulin-like growth factor 2 (IGF-2), endocrine-gland-derived vascular endothelial growth factor), and matrix metalloproteinase system (MMP-9, MMP-14, and tissue inhibitors of metalloproteinase-1). RESULTS: We found that future full-responders have different biomarker profiles than non-responders, while partial-responders cannot be distinguished from either group. When future non-responders were compared to responders, their baseline contained significantly more TGF-beta1, less CD14, and increased level of MMP-9, and concentration of these factors could predict non-responders with high accuracy (AUC = 0.938). Interestingly, during the 38 weeks, levels of MMP-9 decreased in all patients, irrespective of the outcome, while OPG, IGF-2, and TGF-beta1 were higher in non-responders compared to full-responders both at the beginning and the end of the treatment. CONCLUSIONS: The TGF-beta1 and CD14 can distinguish non-responders from responders. The changes in biomarker dynamics during the therapy suggest that growth factors (such as OPG, IGF-2, and TGF-beta) are not markedly influenced by the treatment and that anti-TNF-alpha therapy decreases MMP-9 without influencing the treatment outcome. CI - Copyright (c) 2023 Stepan Coufal et al. FAU - Coufal, Stepan AU - Coufal S AUID- ORCID: 0000-0001-6950-1813 AD - Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. FAU - Kverka, Miloslav AU - Kverka M AD - Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. FAU - Kreisinger, Jakub AU - Kreisinger J AD - Laboratory of Animal Evolutionary Biology, Faculty of Science, Department of Zoology, Charles University, Prague, Czech Republic. FAU - Thon, Tomas AU - Thon T AD - Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. FAU - Rob, Filip AU - Rob F AD - Second Faculty of Medicine, University Hospital Bulovka, Dermatovenerology Department, Charles University, Prague, Czech Republic. FAU - Kolar, Martin AU - Kolar M AD - ISCARE a.s., IBD Clinical and Research Centre, Prague, Czech Republic. FAU - Reiss, Zuzana AU - Reiss Z AD - Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. FAU - Schierova, Dagmar AU - Schierova D AD - Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. FAU - Kostovcikova, Klara AU - Kostovcikova K AD - Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. FAU - Roubalova, Radka AU - Roubalova R AD - Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. FAU - Bajer, Lukas AU - Bajer L AD - Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. AD - Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. FAU - Jackova, Zuzana AU - Jackova Z AD - Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. FAU - Mihula, Martin AU - Mihula M AD - Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. FAU - Drastich, Pavel AU - Drastich P AD - Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. FAU - Tresnak Hercogova, Jana AU - Tresnak Hercogova J AD - Second Faculty of Medicine, University Hospital Bulovka, Dermatovenerology Department, Charles University, Prague, Czech Republic. AD - Dermatology Prof. Hercogova, Center for Biological Therapy, Prague, Czech Republic. FAU - Novakova, Michaela AU - Novakova M AD - Second Faculty of Medicine, University Hospital Bulovka, Dermatovenerology Department, Charles University, Prague, Czech Republic. FAU - Vasatko, Martin AU - Vasatko M AD - ISCARE a.s., IBD Clinical and Research Centre, Prague, Czech Republic. FAU - Lukas, Milan AU - Lukas M AD - ISCARE a.s., IBD Clinical and Research Centre, Prague, Czech Republic. AD - Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Tlaskalova-Hogenova, Helena AU - Tlaskalova-Hogenova H AD - Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. FAU - Jiraskova Zakostelska, Zuzana AU - Jiraskova Zakostelska Z AUID- ORCID: 0000-0002-6695-8188 AD - Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. LA - eng PT - Journal Article DEP - 20230620 PL - Egypt TA - J Immunol Res JT - Journal of immunology research JID - 101627166 RN - 0 (Transforming Growth Factor beta1) RN - 67763-97-7 (Insulin-Like Growth Factor II) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - 0 (Tumor Necrosis Factor Inhibitors) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Humans MH - *Transforming Growth Factor beta1 MH - *Insulin-Like Growth Factor II MH - Matrix Metalloproteinase 9 MH - Tumor Necrosis Factor Inhibitors MH - Vascular Endothelial Growth Factor A PMC - PMC10299888 COIS- The authors declare that they have no conflicts of interest. EDAT- 2023/06/29 13:42 MHDA- 2023/07/03 06:42 PMCR- 2023/06/20 CRDT- 2023/06/29 11:53 PHST- 2023/01/09 00:00 [received] PHST- 2023/05/12 00:00 [revised] PHST- 2023/05/22 00:00 [accepted] PHST- 2023/07/03 06:42 [medline] PHST- 2023/06/29 13:42 [pubmed] PHST- 2023/06/29 11:53 [entrez] PHST- 2023/06/20 00:00 [pmc-release] AID - 10.1155/2023/1535484 [doi] PST - epublish SO - J Immunol Res. 2023 Jun 20;2023:1535484. doi: 10.1155/2023/1535484. eCollection 2023.