Year: 2025
Type: article
Study design: Observational Study
Abstract: AIMS: Sarcoid myopathy (SaM) is characterised by granulomatous myositis (GM) and can overlap with inclusion body myositis (IBM), a late-onset chronic idiopathic inflammatory myopathy with a still enigmatic pathogenesis. As GM can occur in different clinical contexts, we aimed to examine the histomorphologic features and gene expression profiles in cases of definite SaM that may inform diagnostic and therapeutic considerations. METHODS: We performed a multidimensional characterisation of muscle biopsy specimens from patients with 'pure SaM' (n=17), SaM with concomitant IBM (SaM-IBM) (n=2), including histopathologic and ultrastructural analysis in addition to quantitative real-time polymerase chain reaction. Additionally, bulk RNA sequencing was performed on 38 muscle biopsy specimens from patients with SaM (including SaM-IBM) (n=30) and NGI (n=8). RESULTS: Histopathological analysis revealed a pattern of endomysial and perimysial granulomatous inflammation frequently extending to the fascia, endomysial fibrosis, muscle fibre atrophy, variation in muscle fibre size and capillary thickening. Findings from immunohistochemical studies established Chitinase 1 as a pure giant cell marker in SaM. On a subcellular level, 'pure SaM' was characterised by focal accumulation of large swollen mitochondria with rare cristae but an absence of irregular cristae. Transcriptomic analysis of patients with SaM confirmed markedly elevated expression of both type 1 and type 2 human leukocyte antigen molecules. Macrophage activity markers were highly elevated. Consistent with histologic findings, CHIT1 was specifically overexpressed in SaM samples but not in 'pure IBM' muscle biopsy specimens. CONCLUSIONS: SaM is characterised by a stereotypical appearance at the histopathologic level and disease-specific immune dysregulation that involves macrophage function and maturation. SaM-IBM represents a noteworthy overlap syndrome that shares multiple dysregulated immune pathways with 'pure SaM'.
DOI: 10.1111/nan.70040
Authors: Nikolas Ruffer, Iago Pinal‐Fernandez, Felix Kleefeld, Marie‐Therese Holzer, Hans‐Hilmar Goebel, Anne Schänzer, Maria Casal‐Dominguez, Ina Kötter, Norman Görl, Florian Masuhr, Rieke Alten, Eckart Braasch, Albert Grüger, Jörg Müller, Thomas Lempert, Andreas Krause, Tobias B. Huber, Teerin Liewluck, Andrew L. Mammen, Werner Stenzel, Corinna Preusse, Udo Schneider, Martin Krusche
Institutions: Humboldt-Universität zu Berlin, University Medical Center Hamburg-Eppendorf, Charité - Universitätsmedizin Berlin, National Institutes of Health, Johns Hopkins University, National Institute of Arthritis and Musculoskeletal and Skin Diseases, BG University Hospital Bergmannsheil Bochum, Freie Universität Berlin, Ruhr University Bochum, Justus-Liebig-Universität Gießen, Schlosspark-Klinik, Vivantes Klinikum, Immanuel Krankenhaus, Mayo Clinic, Johns Hopkins Medicine
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,480
OpenAlex ID: W4414084775