To construct a comprehensive immune-inflammation-coagulation-fibrinolysis (IICF) network and evaluate its topological features and prognostic value across distinct organ involvement phenotypes in systemic sclerosis.
Approach:
Patient Enrollment: 287 patients with systemic sclerosis were retrospectively enrolled, categorized by organ involvement.
Composite Indices Calculation: Twelve composite indices encompassing IICF pathways were calculated using established methodologies.
Prognostic Score Development: LASSO-Cox regression was used to build a multi-index prognostic score.
Clustering Analysis: K-means clustering was performed to identify molecular endotypes based on the calculated indices.
Survival Analysis: Patients were stratified using optimal cut-off values of the Systemic Immune-Inflammation Index (SII) and the D-dimer-to-Platelet Ratio (DPR) for dual-axis survival analysis.
Key Findings:
Patients with concurrent elevation of both SII and DPR had a 7.41-fold higher mortality risk than those with dual-low levels (HR 7.41, 95% CI 2.09–26.30, P = 0.002).
Elevation of either index alone did not reach statistical significance.
Three IICF molecular endotypes were identified, showing incomplete concordance with the presence of ILD or PH.
The multi-index prognostic score had an area under the curve of 0.747 for mortality prediction.
Interpretation:
Adverse outcomes in systemic sclerosis are driven by systemic network disequilibrium rather than isolated pathway aberrations, highlighting the interplay between immune activation and coagulation dysregulation.
Limitations:
The study is retrospective and conducted at a single center, which may limit the generalizability of the findings.
Echocardiography was used for PH diagnosis, which may not be as definitive as right heart catheterization.
Conclusion:
IICF-based dual-axis stratification and multi-index scoring provide a quantifiable approach for precision phenotyping in systemic sclerosis.
