Integrated Multi-Omics Analysis for Inferring Molecular Players in Inclusion Body Myositis
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 sh...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/8/1639 |
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| author | Judith Cantó-Santos Laura Valls-Roca Ester Tobías Clara Oliva Francesc Josep García-García Mariona Guitart-Mampel Félix Andújar-Sánchez Anna Esteve-Codina Beatriz Martín-Mur Joan Padrosa Raquel Aránega Pedro J. Moreno-Lozano José César Milisenda Rafael Artuch Josep M. Grau-Junyent Glòria Garrabou |
| author_facet | Judith Cantó-Santos Laura Valls-Roca Ester Tobías Clara Oliva Francesc Josep García-García Mariona Guitart-Mampel Félix Andújar-Sánchez Anna Esteve-Codina Beatriz Martín-Mur Joan Padrosa Raquel Aránega Pedro J. Moreno-Lozano José César Milisenda Rafael Artuch Josep M. Grau-Junyent Glòria Garrabou |
| author_sort | Judith Cantó-Santos |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T00:10:09Z |
| format | Article |
| id | doaj.art-0544446c413446e08d5fb26deb02142b |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T00:10:09Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-0544446c413446e08d5fb26deb02142b2023-11-19T00:03:08ZengMDPI AGAntioxidants2076-39212023-08-01128163910.3390/antiox12081639Integrated Multi-Omics Analysis for Inferring Molecular Players in Inclusion Body MyositisJudith Cantó-Santos0Laura Valls-Roca1Ester Tobías2Clara Oliva3Francesc Josep García-García4Mariona Guitart-Mampel5Félix Andújar-Sánchez6Anna Esteve-Codina7Beatriz Martín-Mur8Joan Padrosa9Raquel Aránega10Pedro J. Moreno-Lozano11José César Milisenda12Rafael Artuch13Josep M. Grau-Junyent14Glòria Garrabou15Inherited Metabolic Disorders and Muscular Diseases Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainInherited Metabolic Disorders and Muscular Diseases Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainInherited Metabolic Disorders and Muscular Diseases Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainDepartment of Clinical Biochemistry, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, SpainInherited Metabolic Disorders and Muscular Diseases Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainInherited Metabolic Disorders and Muscular Diseases Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainInherited Metabolic Disorders and Muscular Diseases Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainCNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08028 Barcelona, SpainCNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08028 Barcelona, SpainInherited Metabolic Disorders and Muscular Diseases Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainInherited Metabolic Disorders and Muscular Diseases Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainInherited Metabolic Disorders and Muscular Diseases Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainInherited Metabolic Disorders and Muscular Diseases Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainDepartment of Clinical Biochemistry, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, SpainInherited Metabolic Disorders and Muscular Diseases Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainInherited Metabolic Disorders and Muscular Diseases Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainInclusion 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.https://www.mdpi.com/2076-3921/12/8/1639inclusion body myositis (IBM)metabolismorganic acidsnucleotidesbiomarker |
| spellingShingle | Judith Cantó-Santos Laura Valls-Roca Ester Tobías Clara Oliva Francesc Josep García-García Mariona Guitart-Mampel Félix Andújar-Sánchez Anna Esteve-Codina Beatriz Martín-Mur Joan Padrosa Raquel Aránega Pedro J. Moreno-Lozano José César Milisenda Rafael Artuch Josep M. Grau-Junyent Glòria Garrabou Integrated Multi-Omics Analysis for Inferring Molecular Players in Inclusion Body Myositis Antioxidants inclusion body myositis (IBM) metabolism organic acids nucleotides biomarker |
| title | Integrated Multi-Omics Analysis for Inferring Molecular Players in Inclusion Body Myositis |
| title_full | Integrated Multi-Omics Analysis for Inferring Molecular Players in Inclusion Body Myositis |
| title_fullStr | Integrated Multi-Omics Analysis for Inferring Molecular Players in Inclusion Body Myositis |
| title_full_unstemmed | Integrated Multi-Omics Analysis for Inferring Molecular Players in Inclusion Body Myositis |
| title_short | Integrated Multi-Omics Analysis for Inferring Molecular Players in Inclusion Body Myositis |
| title_sort | integrated multi omics analysis for inferring molecular players in inclusion body myositis |
| topic | inclusion body myositis (IBM) metabolism organic acids nucleotides biomarker |
| url | https://www.mdpi.com/2076-3921/12/8/1639 |
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