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Computational prediction of biomarkers, pathways, and new target drugs in the pathogenesis of immune-based diseases regarding kidney transplantation rejection

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dc.contributor.authorAlfaro, Rafael
dc.contributor.authorMartínez Banaclocha, Helios
dc.contributor.authorLlorente, Santiago
dc.contributor.authorJiménez Coll, Víctor
dc.contributor.authorGalián, José Antonio
dc.contributor.authorBotella, Carmen
dc.contributor.authorMoya Quiles, María Rosa
dc.contributor.authorParrado, Antonio
dc.contributor.authorMuro Pérez, Manuel
dc.contributor.authorMinguela, Alfredo
dc.contributor.authorMuro, Manuel
dc.contributor.authorLegaz Pérez, Isabel
dc.contributor.departmentCiencias Sociosanitarias
dc.date.accessioned2024-07-11T10:52:05Z
dc.date.available2024-07-11T10:52:05Z
dc.date.issued2021-12-15
dc.description© 2021 Alfaro, Martınez-Banaclocha, Llorente, Jimenez-Coll, Galián, Botella, Moya-Quiles, Parrado, Muro-Perez, Minguela, Legaz and Muro. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in Frontiers in Immunology. To access the final edited and published work see https://doi.org/10.3389/fimmu.2021.800968
dc.description.abstractBackground: The diagnosis of graft rejection in kidney transplantation (KT) patients is made by evaluating the histological characteristics of biopsy samples. The evolution of omics sciences and bioinformatics techniques has contributed to the advancement in searching and predicting biomarkers, pathways, and new target drugs that allow a more precise and less invasive diagnosis. The aim was to search for differentially expressed genes (DEGs) in patients with/without antibody-mediated rejection (AMR) and find essential cells involved in AMR, new target drugs, protein-protein interactions (PPI), and know their functional and biological analysis. Material and Methods: Four GEO databases of kidney biopsies of kidney transplantation with/without AMR were analyzed. The infiltrating leukocyte populations in the graft, new target drugs, protein-protein interactions (PPI), functional and biological analysis were studied by different bioinformatics tools. Results: Our results show DEGs and the infiltrating leukocyte populations in the graft. There is an increase in the expression of genes related to different stages of the activation of the immune system, antigenic presentation such as antibody-mediated cytotoxicity, or leukocyte migration during AMR. The importance of the IRF/STAT1 pathways of response to IFN in controlling the expression of genes related to humoral rejection. The genes of this biological pathway were postulated as potential therapeutic targets and biomarkers of AMR. These biological processes correlated showed the infiltration of NK cells and monocytes towards the allograft. Besides the increase in dendritic cell maturation, it plays a central role in mediating the damage suffered by the graft during AMR. Computational approaches to the search for new therapeutic uses of approved target drugs also showed that imatinib might theoretically be helpful in KT for the prevention and/or treatment of AMR. Conclusion: Our results suggest the importance of the IRF/STAT1 pathways in humoral kidney rejection. NK cells and monocytes in graft damage have an essential role during rejection, and imatinib improves KT outcomes. Our results will have to be validated for the potential use of overexpressed genes as rejection biomarkers that can be used as diagnostic and prognostic markers and as therapeutic targets to avoid graft rejection in patients undergoing kidney transplantation.es
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dc.identifier.citationFront. Immunol. 12:800968
dc.identifier.doihttps://doi.org/10.3389/fimmu.2021.800968
dc.identifier.issnElectronic: 1664-3224
dc.identifier.urihttp://hdl.handle.net/10201/143010
dc.languageenges
dc.publisherFrontiers Media
dc.relationOur work was possible thanks to support from Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness. Grant Number PI15/01370, P19/01194, and PI20/00050 and co-funding the European Union with the European Fund of Regional Development (FEDER) with the principle of “A manner to build Europe”es
dc.relation.publisherversionhttps://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.800968/full
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectBioinformatics tooles
dc.subjectBiomarkerses
dc.subjectAcute rejectiones
dc.subjectKidney transplantes
dc.subjectNew target drugses
dc.titleComputational prediction of biomarkers, pathways, and new target drugs in the pathogenesis of immune-based diseases regarding kidney transplantation rejectiones
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublicationb83b4b59-2d61-40f0-9108-5c6a6d158295
relation.isAuthorOfPublication.latestForDiscoveryb83b4b59-2d61-40f0-9108-5c6a6d158295
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