ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0026

Spatial Proteomic-based Phenotyping of Muscle Stem Cells and their Niches in Myositis

Bilgesu Safak Tümerdem1, Yi-Nan Li2, Tim Filla3, Rolf Schröder4, Anna Brunn5, Alexandru Micu6, Ayla Nadja Stuetz1, Laura-Marie Lahu6, Aleix Rius Rigau7, Christina Bergmann8, Alexandru-Emil Matei9, Jörg Distler10 and Andrea-Hermina Györfi11, 1Department of Rheumatology, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University. Hiller Research Center, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University, Düsseldorf, Nordrhein-Westfalen, Germany, 2University Hospital of Düsseldorf, Düsseldorf, Germany, 3Department of Rheumatology, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University. Hiller Research Center, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University., Düsseldorf, Germany, 4Institute of Neuropathology, Friedrich-Alexander University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany, 5Institute of Neuropathology, Heinrich-Heine University, University Hospital of Düsseldorf, Düsseldorf, Germany, 6Department of Rheumatology, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University. Hiller Research Center, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University, Düsseldorf, Germany, 7Department of Internal Medicine 3, Rheumatology and Clinical Immunology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen. Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany, 8Department of Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, 9Department of Rheumatology, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University. Hiller Research Center, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine University. Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, and Fraunhofer Cluster of Excellence for Immune Mediated Diseases CIMD, Frankfurt am Main, Germany, Düsseldorf, Germany, 10University Hospital Duesseldorf and HHU, Duesseldorf, Germany, 11Department of Rheumatology, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University., Düsseldorf, Germany

Meeting: ACR Convergence 2025

Keywords: , , ,

Session Information

Date: Sunday, October 26, 2025

Title: (0019–0048) Genetics, Genomics & Proteomics Poster

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Immune-mediated inflammatory myopathies (IIMs) are a heterogeneous group of diseases characterized by chronic inflammation, damage and impaired regeneration of the skeletal muscle leading to progressive muscle weakness. Muscle stem cells (MuSCs) play a key role in muscle regeneration, together with other myogenic and non-myogenic stromal cells. However, the exact mechanisms of impaired skeletal muscle regeneration in IIMs are incompletely understood.

Methods: We applied imaging mass cytometry (IMC) to explore the heterogeneity of MuSCs at the single-cell level and characterize cellular alterations of MuSC niches in situ in muscle biopsies of IIM patients. Muscle biopsies of patients with dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), and control individuals (CO) were analyzed.

Results: We analyzed a total of 69288 cells, including 57623 stromal cells, of which 14595 MuSCs, and identified 17 stromal cell subpopulations, including four subpopulations of MuSCs. We observed IIM-subtype-specific changes in the frequencies of MuSC subpopulations. CD56hi;CD90hi;PAX7low MuSCs were particularly upregulated in PM and DM, while CD82hi;PAX7low MuSCs were mostly upregulated in IBM muscle biopsies. GLI1hi;PAX7hi MuSCs were upregulated only in PM patients and CD82neg;PAX7low MuSCs were not changed in frequency compared with CO. Each MuSC subpopulation was characterized by a unique spatial niche. Two MuSC niches were enriched for distinct stromal cells (CD82hi;PAX7low and CD82neg;PAX7low MuSC niches) and the other two (CD56hi;CD90hi;PAX7low and GLI1hi;PAX7hi MuSC niches) for distinct subsets of immune cells. The CD82hi;PAX7low MuSC niche was composed of LECs, while the CD82neg;PAX7low MuSC niche was composed of ECs and muscle fibers. The CD56hi;CD90hi;PAX7low MuSC cellular neighborhood (CN) was enriched in NK cells, HLA-DR- M2 macrophages, and regenerating muscle fibers, while the GLI1hi;PAX7hi MuSC CN was enriched in HLA-DR+ M2 macrophages, HLA-DR+ CD20+ B cells, HLA-DR+ CD28- T cells, and helper T cells. Furthermore, we identified IIM-subtype-specific perturbations in the cellular interaction network of MuSC populations. The frequencies of MuSC subpopulations correlated with standard histopathological measures of muscle regeneration.

Conclusion: Using spatial proteomics, we unraveled the heterogeneity of MuSCs in DM, PM and IBM patients and identified IIM-subtype-specific changes in the frequencies of the distinct MuSC subpopulations together with unique perturbations in their local niches and cellular interactions. These data might offer potential for therapeutic modulation of individual MuSC subpopulations in IIM, aiming to improve skeletal muscle regeneration and thus combat disabling muscle weakness.

Disclosures: B. Tümerdem: None; Y. Li: None; T. Filla: None; R. Schröder: None; A. Brunn: None; A. Micu: None; A. Stuetz: None; L. Lahu: None; A. Rius Rigau: None; C. Bergmann: Kyverna Therapeutics, Inc., 5; A. Matei: None; J. Distler: 4D Science, 8, 11, Actelion, 2, 6, Active Biotech, 2, 6, Anamar, 2, 6, Array Biopharma, 2, 6, ARXX Therapeutics, 2, 6, aTyr Pharma, 2, 6, Bayer Pharma, 2, 6, BMS (Bristol-Myers Squibb), 2, 6, Boehringer Ingelheim, 2, 6, Celgene, 2, 6, FibroCure, 4, Galapagos, 2, 6, GSK, 2, 6, Inventiva, 2, 6, JB Therapeutics, 2, 6, Medac, 2, 6, Novartis, 2, 6, Pfizer, 2, 6, Redx Pharma, 2, 6, RuiYi, 2, 6, Sanofi-Aventis, 2, 6, UCB, 2, 6; A. Györfi: AbbVie, 6, Boehringer-Ingelheim, 6.

To cite this abstract in AMA style:

Tümerdem B, Li Y, Filla T, Schröder R, Brunn A, Micu A, Stuetz A, Lahu L, Rius Rigau A, Bergmann C, Matei A, Distler J, Györfi A. Spatial Proteomic-based Phenotyping of Muscle Stem Cells and their Niches in Myositis [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/spatial-proteomic-based-phenotyping-of-muscle-stem-cells-and-their-niches-in-myositis/. Accessed .

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