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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 \u03b2 peptide 1\u201342 (A\u03b21\u201342) 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.<\/jats:p>","DOI":"10.3390\/antiox12081639","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T01:33:11Z","timestamp":1692581591000},"page":"1639","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrated Multi-Omics Analysis for Inferring Molecular Players in Inclusion Body Myositis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0272-7014","authenticated-orcid":false,"given":"Judith","family":"Cant\u00f3-Santos","sequence":"first","affiliation":[{"name":"Inherited Metabolic Disorders and Muscular Diseases Research Group, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University 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Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1093\/rheumatology\/keab716","article-title":"Survival and Associated Comorbidities in Inclusion Body Myositis","volume":"61","author":"Naddaf","year":"2022","journal-title":"Rheumatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9091","DOI":"10.15252\/emmm.201809091","article-title":"Metabolomes of Mitochondrial Diseases and Inclusion Body Myositis Patients: Treatment Targets and Biomarkers","volume":"10","author":"Buzkova","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e12931","DOI":"10.1111\/bpa.12931","article-title":"Mitochondrial DNA Variants in Inclusion Body Myositis Characterized by Deep Sequencing","volume":"31","author":"Lindgren","year":"2021","journal-title":"Brain Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1042\/CS20160080","article-title":"Mitochondrial DNA Disturbances and Deregulated Expression of Oxidative Phosphorylation and Mitochondrial Fusion Proteins in Sporadic Inclusion Body Myositis","volume":"130","author":"Garrabou","year":"2016","journal-title":"Clin. 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