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

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.