Objective:

To characterize immune network dysregulation in RA and SLE using an integrated analytical framework and evaluate their relevance for precision medicine.

Approach:

• Study Design: Retrospective observational study including 875 patients (RA: 450; SLE: 425) diagnosed between January 2021 and December 2025.
• Cytokine Measurement: Cytokine levels were measured using multiplex immunoassays and normalized to z-scores.
• Autoantibody Profiling: Validated assays were used to determine autoantibody profiles.
• Data Analysis: Correlation analysis, multivariate regression, PCA, and hierarchical clustering were applied to identify immune interactions and sub-phenotypes.

Key Findings:

• Distinct immune signatures were observed for RA and SLE.
• Pro-inflammatory cytokines IL-6 and IL-17 were elevated in RA and correlated with disease activity (r = 0.48 and r = 0.42, respectively).
• In SLE, IFN-γ and MCP-1 were associated with disease activity and organ involvement (r = 0.51 and r = 0.52).
• Autoantibody profiles differed significantly between RA and SLE.
• Cytokines were independent predictors of disease activity, while autoantibody burden showed limited predictive value (p = 0.08).

Interpretation:

Integrated immune profiling reveals both shared and distinct immune dysregulation in RA and SLE.

Limitations:

• The study is retrospective and observational, which may limit causal inferences.
• The sample size, while substantial, may not capture all variations in immune responses.

Conclusion:

Cytokine signatures are key biomarkers for patient stratification and precision medicine in RA and SLE.