Integrative Molecular Analyses of Inflammatory and Autoimmune Signals in Cardiac Sarcoidosis - PubMed
2 hours ago
- #cardiac_sarcoidosis
- #autoimmunity
- #transcriptomics
- Single-cell and spatial transcriptomic analyses reveal distinct cellular and gene expression profiles in preserved, granulomatous, and fibrotic regions of cardiac sarcoidosis (CS) hearts.
- Cardiomyocytes upregulate arrhythmogenic and inflammasome transcripts, while fibroblasts and cardiomyocytes produce chemoattractant cytokines that sustain immune cell infiltration.
- Granulomas contain macrophages with cell-cell fusion modulators and Th17-skewed T cells that promote B-cell activation and antibody production via B-cell-activating factor.
- Fibrotic regions feature tertiary lymphoid structures with clonally expanded mature B and plasma cells, producing autoantibodies reactive to cardiac proteins like periplakin (PPL).
- Identification of PPL as a CS autoantigen may explain shared clinical features with desmosomal cardiomyopathies and offers therapeutic targets to limit granuloma formation and B-cell activation.