Systemic and Tissue Inflammation in Juvenile Dermatomyositis: From Pathogenesis to the Quest for Monitoring Tools

Abstract

Juvenile Dermatomyositis (JDM) is a systemic immune-mediated disease of childhood, characterized by muscle weakness, and a typical skin rash. Other organ systems and tissues such as the lungs, heart, and intestines can be involved, but may be under-evaluated. The inflammatory process in JDM is characterized by an interferon signature and infiltration of immune cells such as T cells and plasmacytoid dendritic cells into the affected tissues. Vasculopathy due to loss and dysfunction of endothelial cells as a result of the inflammation is thought to underlie the symptoms in most organs and tissues. JDM is a heterogeneous disease, and several disease phenotypes, each with a varying combination of affected tissues and organs, are linked to the presence of myositis autoantibodies. These autoantibodies have therefore been extensively studied as biomarkers for the disease phenotype and its associated prognosis. Next to identifying the JDM phenotype, monitoring of disease activity and disease-inflicted damage not only in muscle and skin, but also in other organs and tissues, is an important part of clinical follow-up, as these are key determinants for the long-term outcomes of patients. Various monitoring tools are currently available, among which clinical assessment, histopathological investigation of muscle and skin biopsies, and laboratory testing of blood for specific biomarkers. These investigations also give novel insights into the underlying immunological processes that drive inflammation in JDM and suggest a strong link between the interferon signature and vasculopathy. New tools are being developed in the quest for minimally invasive, but sensitive and specific diagnostic methods that correlate well with clinical symptoms or reflect local, low-grade inflammation. In this review we will discuss the types of (extra)muscular tissue inflammation in JDM and their relation to vasculopathic changes, critically assess the available diagnostic methods including myositis autoantibodies and newly identified biomarkers, and reflect on the immunopathogenic implications of identified markers.

Crosstalk Between Innate and T Cell Adaptive Immunity With(in) the Muscle

“…Two different types of dendritic cells have been described in the muscle infiltrates of IIM patients, with a predominance of plasmocytoid DCs in dermatomyositis, and monocyte-derived DCs in polymyositis and inclusion body myositis (Pimorady-Esfahani et al, 1997;Wienke et al, 2018).…”

Serum protein biomarkers for juvenile dermatomyositis: a pilot study

“…In this context, blood accessible biomarkers are becoming attractive because they are less invasive, objectively measurable, inexpensive, and can be employed as surrogate outcome measures if validated. A set of blood accessible biomarkers, primarily those associated with muscle damage such as creatine kinase (CK), aldolase A (ALDOA), lactate dehydrogenase (LDH), alanine transaminase (ALT), and aspartate aminotransferase (AST) have been previously defined and are currently used in combination with other clinical outcomes to assess disease activity in JDM [18]. These biomarkers indicate muscle damage and are often influenced by exercise and, therefore, may not be specific to assess disease activity.…”

Juvenile Dermatomyositis and the Inflammatory Myopathies

“…7 Whether genetically destined or provoked by an environmental or infectious process, an immune-mediated inflammatory cascade is triggered, leading to a systemic vasculopathy affecting the endothelial cells in the majority of a patient's tissues. 8 Early in the disease course, cytokines and interferons cause a small vessel vasculitis. 9 Over time, however, inflammatory products occlude the vessels, leading to capillary destruction and surrounding tissue necrosis.…”