A dynamic vascular-inflammatory-fibrotic loop in systemic sclerosis: an integrative immuno-vascular framework

Area of Science:

• Rheumatology and Immunology
• Vascular Biology
• Fibrosis Research

Background:

• Systemic sclerosis (SSc) exhibits complex heterogeneity, involving vascular dysfunction, immune activation, and fibrosis.
• Current therapeutic strategies for SSc show inconsistent and transient responses, indicating underlying dynamic disease processes.
• Disease persistence in SSc likely stems from intricate interactions between pathogenic pathways, not isolated mechanisms.

Purpose of the Study:

• To propose a novel conceptual framework for Systemic sclerosis (SSc).
• Integrate vascular, immune, and fibrotic processes into a dynamic loop model for SSc.
• Derive the model from longitudinal clinical observations and existing literature.

Main Methods:

• Longitudinal clinical follow-up of SSc cohorts.
• Nailfold videocapillaroscopy pattern analysis.
• Immune biomarker profiling and outcome analysis.

Main Results:

• Systemic sclerosis (SSc) is modeled as a self-sustaining dynamic loop of interacting vascular, immune, and fibrotic pathways.
• Capillaroscopy patterns indicate disease phase, while biomarkers reflect functional states.
• The model explains clinical heterogeneity and limited durability of single-target treatments.

Conclusions:

• Systemic sclerosis (SSc) is a dynamic system with shifting pathway dominance within a persistent loop.
• This dynamic loop model unifies the interpretation of SSc heterogeneity.
• The framework supports developing stage-adapted, combination therapeutic strategies for SSc.