Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis

Per-Ole Carstens; Luisa M Müllar; Arne Wrede; Sabrina Zechel; Martin M Wachowski; Almuth Brandis; Sabine Krause; Stephan Zierz; Jens Schmidt

doi:10.3389/fimmu.2023.1177721

Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis

Front Immunol. 2023 Sep 5:14:1177721. doi: 10.3389/fimmu.2023.1177721. eCollection 2023.

Authors

Per-Ole Carstens¹, Luisa M Müllar¹, Arne Wrede^{2

3}, Sabrina Zechel², Martin M Wachowski⁴, Almuth Brandis^{5

6}, Sabine Krause⁷, Stephan Zierz⁸, Jens Schmidt^{1

9

10}

Affiliations

¹ Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
² Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
³ Institute of Neuropathology, Saarland University Medical Center and Medical Faculty of Saarland University, Homburg, Germany.
⁴ Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Göttingen, Göttingen, Germany.
⁵ Department of Pathology, Klinikum Region Hannover, Hannover, Germany.
⁶ Institute of Pathology and Neuropathology, Medical University Hannover, Hannover, Germany.
⁷ Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of München, München, Germany.
⁸ Department of Neurology, University Hospital Halle/Saale, Halle, Germany.
⁹ Department of Neurology and Pain Treatment, Neuromuscular Center, Center for Translational Medicine, Immanuel Klinik Rüdersdorf, University Hospital of the Brandenburg Medical School Theodor Fontane, Rüdersdorf bei Berlin, Germany.
¹⁰ Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, Rüdersdorf bei, Berlin, Germany.

Abstract

Introduction: We aimed to identify B-cell-mediated immunomechanisms in inclusion body myositis (IBM) and polymyositis (PM) as part of the complex pathophysiology.

Materials and methods: Human primary myotube cultures were derived from orthopedic surgery. Diagnostic biopsy specimens from patients with IBM (n=9) and PM (n=9) were analyzed for markers of B cell activation (BAFF and APRIL) and for chemokines that control the recruitment of B cells (CXCL-12 and CXCL-13). Results were compared to biopsy specimens without myopathic changes (n=9) and hereditary muscular dystrophy (n=9).

Results: The mRNA expression of BAFF, APRIL, and CXCL-13 was significantly higher in IBM and PM compared to controls. Patients with IBM displayed the highest number of double positive muscle fibers for BAFF and CXCL-12 (48%) compared to PM (25%), muscular dystrophy (3%), and non-myopathic controls (0%). In vitro, exposure of human myotubes to pro-inflammatory cytokines led to a significant upregulation of BAFF and CXCL-12, but APRIL and CXCL-13 remained unchanged.

Conclusion: The results substantiate the hypothesis of an involvement of B cell-associated mechanisms in the pathophysiology of IBM and PM. Muscle fibers themselves seem to contribute to the recruitment of B cells and sustain inflammation.

Keywords: B cells; autoimmune diseases; inflammatory muscle disease; myositis; neuromuscular disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Inflammation
Muscle Fibers, Skeletal
Myositis*
Myositis, Inclusion Body*
Polymyositis*

Grants and funding

The study was supported in part by the AFM (Association Française contre les Myopathies, grant no. 20987) and by intramural funds from the University Medical Center Göttingen (Forschungsförderprogramm). The Open Access Publication Funds of the Göttingen University is gratefully acknowledged. The funder was not involved in the study design, collection, analysis, interpretation of data, writing of this article, or the decision to submit it for publication.