Dataset Information

Proteomic Profiles in Inclusion Body Myositis and Polymyositis with Mitochondrial Pathology: A Comparative Study Across Idiopathic Inflammatory Myopathies

ABSTRACT: Idiopathic inflammatory myopathies (IIMs) encompass a diverse group of autoimmune disorders affecting skeletal muscle, including dermatomyositis (DM), anti-synthetase syndrome (ASyS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Polymyositis with mitochondrial pathology (PM-Mito) has been proposed as a potential IIM subtype, with emerging evidence suggesting it may represent an early form of IBM. IBM is characterized by unique clinical features, such as insidious onset and resistance to immunotherapies, alongside hallmark histopathological findings, including rimmed vacuoles, cytoplasmic protein aggregates, CD8+ T cell-dominated inflammation, and prominent mitochondrial abnormalities. Mitochondrial dysfunction, ragged-red fibers, and disrupted oxidative phosphorylation are increasingly recognized as central contributors to IBM pathology, implicating mitochondrial processes in both muscle weakness and chronic inflammation. This study presents a longitudinal and cross-sectional proteomic analysis of IBM in comparison to other IIM subtypes. We identified both established and novel hallmarks of IBM, particularly highlighting mitochondrial dysfunction and immune dysregulation, while also examining PM-Mito as a potential precursor state to IBM. Using an unbiased mass spectrometry-based proteomic approach, we identified a distinct proteomic signature for IBM characterized by mitochondrial alterations and type II interferon-associated immune pathway dysregulation. PM-Mito samples displayed a dysregulation of immune regulatory proteins and mitochondrial pathways. This study reinforces the unique molecular profile of IBM compared to other IIM subtypes while strengthening the concept of a disease continuum between IBM and PM-Mito. By uncovering shared mitochondrial and immune dysregulation in IBM and PM-Mito, these findings support the notion that PM-Mito may represent an early or transitional stage of IBM, providing new insights into disease progression and potential therapeutic targets.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Felix Kleefeld

PROVIDER: PXD063841 | JPOST Repository | Tue May 12 00:00:00 GMT+01:00 2026

REPOSITORIES: jPOST

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			Action	DRS
	O220902_033_S2-C2_1_4558.d.zip	Other
	O220907_007_S2-A1_1_4718.d.zip	Other
	O220907_008_S2-A2_1_4719.d.zip	Other
	O220907_009_S2-A3_1_4720.d.zip	Other
	O220907_010_S2-A4_1_4721.d.zip	Other

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Dataset Information

Proteomic Profiles in Inclusion Body Myositis and Polymyositis with Mitochondrial Pathology: A Comparative Study Across Idiopathic Inflammatory Myopathies

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