Muscle Spatial Transcriptomic Reveals Heterogeneous Profiles in Juvenile Dermatomyositis and Persistence of Abnormal...

Area of Science:

• Muscle biology
• Immunology
• Genetics

Background:

• Juvenile dermatomyositis (JDM) is an autoimmune disease affecting muscles.
• Understanding the molecular basis of JDM muscle pathology is crucial for effective treatment and management.

Purpose of the Study:

• To investigate the spatial heterogeneity of molecular signatures in JDM muscle before and after treatment.
• To identify novel genes and pathways associated with JDM pathophysiology.
• To explore the potential of these signatures as biomarkers for disease relapse.

Main Methods:

• Spatial transcriptomics and standardized morphometry were used on JDM muscle biopsies.
• Unsupervised reference-free deconvolution identified molecular signatures.
• Signatures were scored in biopsies from before and after remission.

Main Results:

• A normal muscle signature related to mitochondrial biology disappeared in JDM patients.
• Three pathological signatures were identified: "myofibrillar stress", "muscle remodeling", and "interferon signaling".
• The "myofibrillar stress" signature correlated with disease severity, while "muscle remodeling" was linked to a better outcome. Novel genes ANKRD1 and FSLT1 were identified.
• Pathological signatures persisted in muscle tissue two years after remission.

Conclusions:

• JDM muscle exhibits spatially distinct molecular signatures.
• These signatures, particularly "myofibrillar stress" and "interferon signaling", persist post-treatment.
• Persistent signatures may serve as biomarkers for predicting JDM relapse and understanding disease pathophysiology.