Integrated transcriptomic and epigenomic profiling reveals conserved molecular subtypes across systemic autoimmune diseases - PubMed
4 hours ago
- #molecular subtypes
- #multi-omics
- #autoimmune diseases
- Integrative multi-omics analyses identified two conserved molecular subtypes across rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjögren's syndrome (pSS): megakaryocyte-enriched and B-cell-enriched subtypes.
- The megakaryocyte-enriched subtype is associated with higher platelet counts, increased disease activity, and broader organ involvement.
- Epigenomic profiling revealed distinct chromatin accessibility and super-enhancer landscapes linked to subtype-specific genes (e.g., ZFP36L1 and RAD51B for megakaryocyte-enriched; MAF and PRDM1 for B-cell-enriched).
- Single-cell RNA sequencing confirmed the expansion of platelet-producing megakaryocytes in the megakaryocyte-enriched subtype and enhanced B-cell activation in the B-cell-enriched subtype.
- The findings suggest these conserved subtypes could inform precision stratification and lineage-targeted therapies for systemic autoimmune diseases.