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

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1177721

DOI=10.3389/fimmu.2023.1177721

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>We aimed to identify B-cell-mediated immunomechanisms in inclusion body myositis (IBM) and polymyositis (PM) as part of the complex pathophysiology.</p></sec><sec><title>Materials and methods</title><p>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).</p></sec><sec><title>Results</title><p>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%). <italic>In vitro</italic>, 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.</p></sec><sec><title>Conclusion</title><p>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.</p></sec>