Proteomics Analysis of Plasma-Derived Exosomes Unveils the Aberrant Complement and Coagulation Cascades in Dermatomyositis/Polymyositis

Dermatomyositis and polymyositis (DM/PM) are systemic
autoimmune
diseases characterized by proximal muscle weakness. The underlying
pathogenetic mechanism of this disease remains under-researched. Here,
using proteomics analysis, a great overlap of differentially expressed
plasma exosomal proteins involved in the complement and coagulation
cascade pathway, including FGA, FGB, FGG, C1QB, C1QC, and VWF, was
identified in DM/PM patients versus healthy controls. Correlation
analysis showed that the expression levels of complement-associated
proteins (C1QB and C1QC) correlated positively with CRP, ESR, and
platelet count. ROC curve analysis demonstrated that complement and
coagulation cascade-associated proteins could be strong predictors
for DM/PM. In addition, we also identified several other proteins
that were differentially expressed in DM and PM. The selected candidate
proteins were further validated by parallel reaction monitoring (PRM)
and enzyme-linked immunosorbent assay (ELISA). Together, our findings
indicate that these exosome-derived proteins might participate in
microvascular damage in DM/PM through the activation of the complement
and coagulation cascade pathway and function as biomarkers for the
clinical diagnosis of DM/PM.