TY - JOUR
T1 - Systemic and Tissue Inflammation in Juvenile Dermatomyositis
T2 - From Pathogenesis to the Quest for Monitoring Tools
AU - Wienke, Judith
AU - Deakin, Claire T.
AU - Wedderburn, Lucy R.
AU - van Wijk, Femke
AU - van Royen-Kerkhof, Annet
N1 - Publisher Copyright:
© Copyright © 2018 Wienke, Deakin, Wedderburn, van Wijk and van Royen-Kerkhof.
PY - 2018/12/18
Y1 - 2018/12/18
N2 - 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.
AB - 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.
KW - autoantibodies
KW - biomarkers
KW - disease monitoring
KW - interferon signature
KW - juvenile dermatomyositis
KW - personalized medicine
KW - tissue inflammation
KW - vasculopathy
UR - http://www.scopus.com/inward/record.url?scp=85059927481&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2018.02951
DO - 10.3389/fimmu.2018.02951
M3 - Review article
C2 - 30619311
AN - SCOPUS:85059927481
SN - 1664-3224
VL - 9
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 2951
ER -