Integrated multi-omics analysis for inferring molecular players in inclusion body myositis

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• dc.contributor.author Cantó-Santos, Judith
• dc.contributor.author Valls-Roca, Laura
• dc.contributor.author Tobías, Ester
• dc.contributor.author Oliva, Clara
• dc.contributor.author García-García, Francesc Josep
• dc.contributor.author Guitart-Mampel, Mariona
• dc.contributor.author Andújar-Sánchez, Félix
• dc.contributor.author Esteve-Codina, Anna
• dc.contributor.author Martín-Mur, Beatriz
• dc.contributor.author Padrosa, Joan
• dc.contributor.author Aránega, Raquel
• dc.contributor.author Moreno-Lozano, Pedro J.
• dc.contributor.author Milisenda, José César
• dc.contributor.author Artuch, Rafael
• dc.contributor.author Grau-Junyent, Josep M.
• dc.contributor.author Garrabou, Glòria
• dc.date.accessioned 2023-12-18T07:05:22Z
• dc.date.available 2023-12-18T07:05:22Z
• dc.date.issued 2023
• dc.description.abstract Inclusion body myositis (IBM) is an acquired inflammatory myopathy affecting proximal and distal muscles that leads to weakness in patients over 50. It is diagnosed based on clinical and histological findings in muscle related to inflammation, degeneration, and mitochondria. In relation to IBM, a shortage of validated disease models and a lack of biomarkers and effective treatments constitute an unmet medical need. To overcome these hurdles, we performed an omics analysis of multiple samples from IBM patients (saliva, fibroblasts, urine, plasma, and muscle) to gain insight into the pathophysiology of IBM. Degeneration was evident due to the presence of amyloid β peptide 1-42 (Aβ1-42) in the saliva of the analyzed IBM patients. The presence of metabolic disarrangements in IBM was indicated by an imbalanced organic acid profile in fibroblasts and urine. Specifically, abnormal levels of L-pyroglutamic and orotic acid were supported by the abnormal expression of related metabolites in plasma and urine (glutathione and pyrimidines) and the aberrant expression of upstream gene regulators (L2HGDH, IDH2, OPLAH, and ASL) in muscle. Combined levels of L-pyroglutamic and orotic acid displayed an outstanding biomarker signature in urine with 100% sensitivity and specificity. The confirmation of systemic metabolic disarrangements in IBM and the identification of novel biomarkers reported herein unveil novel insights that require validation in larger cohorts.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cantó-Santos J, Valls-Roca L, Tobías E, Oliva C, García-García FJ, Guitart-Mampel M, Andújar-Sánchez F, Esteve-Codina A, Martín-Mur B, Padrosa J, Aránega R, Moreno-Lozano PJ, Milisenda JC, Artuch R, Grau-Junyent JM, Garrabou G. Integrated multi-omics analysis for inferring molecular players in inclusion body myositis. Antioxidants (Basel). 2023 Aug 19;12(8):1639. DOI: 10.3390/antiox12081639
• dc.identifier.doi http://dx.doi.org/10.3390/antiox12081639
• dc.identifier.issn 2076-3921
• dc.identifier.uri http://hdl.handle.net/10230/58562
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof Antioxidants (Basel). 2023 Aug 19;12(8):1639
• dc.rights © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Biomarker
• dc.subject.keyword Inclusion body myositis (IBM)
• dc.subject.keyword Metabolism
• dc.subject.keyword Nucleotides
• dc.subject.keyword Organic acids
• dc.title Integrated multi-omics analysis for inferring molecular players in inclusion body myositis
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion