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Current Concepts on the Pathogenesis of Systemic Sclerosis.

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Area of Science:

  • Immunology
  • Pathology
  • Genetics

Background:

  • Systemic sclerosis (SSc) is a fibrotic autoimmune disease with variable clinical outcomes, often impacting lungs and heart.
  • The disease affects women more frequently, with pathogenesis involving genetic predisposition, environmental triggers, and epigenetic modifications.

Purpose of the Study:

  • To explore the complex pathogenetic mechanisms underlying systemic sclerosis (SSc).
  • To highlight the heterogeneity in cell differentiation and functional states within SSc.
  • To identify distinct pathogenic mechanisms for patient subgrouping and personalized treatment.

Main Methods:

  • Review of clinical characteristics, pathogenesis, and recent multi-omics studies in SSc.
  • Analysis of immune-inflammatory dysregulation, endothelial cell behavior, and myofibroblast differentiation.
  • Integration of single-cell RNA sequencing and systems biology approaches.

Main Results:

  • SSc pathogenesis involves immune dysregulation, altered endothelial cells, and myofibroblast trans-differentiation.
  • Profibrotic signaling pathways (e.g., TGF-β) and immune responses contribute to disease.
  • Single-cell and multi-omics data reveal significant cellular heterogeneity in SSc.

Conclusions:

  • SSc exhibits profound heterogeneity in cellular states and pathogenic mechanisms.
  • Systems biology approaches are crucial for subgrouping SSc patients.
  • Deciphering this heterogeneity is essential for developing personalized therapeutic strategies for SSc.