A Preclinical State of Graves' Ophthalmopathy Characterized by Hypoxia of T-cells Identified via Multiomics Analysis.
Summary
Multi-omics integration (DIABLO) distinguished a preclinical GO state with near-perfect accuracy, revealing hypoxia-pathway enrichment and hypoxia-driven skewing of effector CD4+ subsets (Th1, Th17, CD4+ CTL). This provides mechanistic insight and potential early biomarkers to intervene before overt ophthalmopathy.
Key Findings
- DIABLO accurately discriminated pre-GO from GH/GO using 17 DMCs and 11 DEGs (ROC ≈ 0.9975 and 0.9407).
- Pre-GO displayed hypoxia pathway enrichment among specific DEGs.
- Hypoxia promoted Th1, Th17, and antigen-specific CD4+ cytotoxic T-cell differentiation by flow cytometry.
Clinical Implications
Potential for early risk stratification in Graves’ hyperthyroidism using peripheral blood multi-omic signatures; hypoxia pathway targeting (e.g., metabolic or microenvironmental modulation) may prevent progression to overt ophthalmopathy.
Why It Matters
Identifying a mechanistically defined preclinical state in GO bridges diagnosis and prevention, highlighting hypoxia as a modifiable axis for early intervention.
Limitations
- Relatively small sample size across groups limits generalizability
- Cross-sectional omics snapshots require prospective validation for prediction
Future Directions
Prospective validation of pre-GO signatures to predict GO onset; interventional trials testing hypoxia-modulating strategies to prevent GO progression.
Study Information
- Study Type
- Case-control
- Research Domain
- Pathophysiology
- Evidence Level
- III - Multi-omics case-control analysis with functional in vitro validation.
- Study Design
- OTHER