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Progression from at-risk state to clinical and severe systemic lupus erythematosus involves molecular dysregulations potentially reversible by biologics: implications for early diagnosis and treatment

5 days ago
  • #systemic lupus erythematosus
  • #biologics
  • #early diagnosis
  • Progression from at-risk state to clinical and severe systemic lupus erythematosus (SLE) involves molecular dysregulations.
  • Transcriptomic changes were explored during progression from preclinical to clinical and advanced SLE.
  • At-risk individuals showed deregulated metabolic, cytokine signalling, haematologic, and stress-response pathways.
  • Progressors exhibited heightened interferon (IFN)-alpha/gamma and inflammatory cytokine activity.
  • A 17-gene susceptibility signature predicted transition to SLE with an area under the curve of 0.80.
  • Stepwise upregulation of IFN-α/γ, haem metabolism, and oxidative phosphorylation pathways was observed.
  • SLE susceptibility and progression signatures demonstrated potential reversibility by biologics like anifrolumab and belimumab.
  • Blood molecular profiling may aid risk stratification and early biologic intervention.