Pathogenesis of systemic sclerosis-current concept and emerging treatments

Area of Science:

• Immunology
• Pathology
• Rheumatology

Background:

• Systemic sclerosis (SSc) is a complex, high-mortality disease with poorly understood pathogenesis.
• Key features include autoimmunity, vasculopathy, and fibrosis, driven by activated B cells and autoantibodies.
• Autoantibodies targeting endothelial cells contribute to inflammation and fibrosis in SSc.

Purpose of the Study:

• To review recent advancements in understanding SSc pathogenesis.
• To discuss the roles of autoantibodies, vasculopathy, and fibrosis.
• To summarize animal models and emerging therapeutic strategies for SSc.

Main Methods:

• Literature review of recent studies on SSc pathogenesis.
• Analysis of the role of B cells, autoantibodies, and profibrotic cytokines.
• Examination of animal models and novel treatment approaches.

Main Results:

• B cells in SSc are constitutively activated, producing various autoantibodies, including diagnostic biomarkers and functional autoantibodies against endothelial cells.
• Autoantibody-induced endothelial cell damage promotes inflammation and fibroblast activation.
• Profibrotic cytokines like TGF-β, CTGF, IL-4/IL-13, and IL-6 are critical for collagen production.

Conclusions:

• Targeting causative molecules like autoantibodies and profibrotic cytokines holds promise for improving SSc patient outcomes.
• Further research into SSc pathogenesis, including animal models, is essential for developing effective therapies.
• Emerging treatments focusing on specific molecular pathways may offer new hope for managing this intractable disease.