Pathogenesis of myositis in children

There is increasing evidence for involvement of innate immune mechanisms in the pathogenesis of idiopathic inflammatory myopathies. This review focuses on recent advances in understanding these mechanisms in juvenile dermatomyositis, the most common form of childhood inflammatory myopathy.

Type I interferon activity in juvenile dermatomyositis has been demonstrated by both global gene expression profiling and immunohistochemical analysis of affected tissues. Most recently, expression of interferon-inducible genes in peripheral blood cells has shown promise as a biomarker for disease activity. The possible pathogenic actions of type I interferons include induction and maintenance of major histocompatibility complex class I expression in affected myofibers, and promotion of local pro-inflammatory cytokine and chemokine production. The cellular source of type I interferons is not clearly defined, though plasmacytoid dendritic cells that constitute a significant component of the inflammatory cell infiltrate are obvious candidates. These cells likely contribute to pathogenesis not only via type I interferon production, but also by regulating other infiltrating inflammatory cells.

Type I interferons and plasmacytoid dendritic cells appear to make important contributions to the pathogenesis of juvenile dermatomyositis. Understanding the role of the innate immune system in childhood myositis may lead to novel treatment strategies.