Dr. med. Christopher Nelke (Düsseldorf / DE), Dr. rer. nat. Corinna Preuße (Berling / DE), Dr. Kathrin Koch (Düsseldorf / DE), Derya Cengiz (Düsseldorf / DE), Vera Dobelmann (Düsseldorf / DE), Univ.-Prof. Dr. med. Dr. rer. nat. Sven G. Meuth (Düsseldorf / DE), Prof. Dr. med Werner Stenzel (Berling / DE), PD Dr. med. Tobias Ruck (Düsseldorf / DE)
Abstract-Text (inkl. Referenzen)
Background
Management of inclusion body myositis (IBM) is challenging. Contemporary strategies mostly employ immunosuppression. As these approaches were largely unable to halt disease progression, we hypothesize that cell-autonomous mechanisms might contribute to IBM pathophysiology. This viewpoint places autoimmunity at the disease onset, initiating complex changes at the cellular level ultimately sustaining disease progression. Aiming to characterize these changes, we studied cellular senescence in IBM muscle.
Methods
We acquired and isolated primary human muscle cells (PHMC) from non-diseased controls and IBM patients. After cultivation, these cells were stained with senescence-associated β-galactosidase (SA-βgal). SA-βgal activity is considered a biomarker of cellular senescence. For quantification, PHMC were stained with a fluorescence SA-βgal antibody and SA-βgal+ PHMC were measured by flow cytometry. p16INK4A expression, another marker for cellular senescence, was measured by quantitative real-time PCR in skeletal muscle specimens.
Results
Our key findings are:
- PHMC from IBM patients display elevated SA-βgal as evidenced by light microscopy and quantification using flow cytometry. - p16INK4A RNA level were substantially elevated in IBM patients as compared to NDC.Conclusion
Our data provides preliminary evidence for cellular senescence as prominent feature in IBM. Further studies are needed to understand the molecular underpinnings and specificity of this finding.