Exploration of Immunology

Table 3. Disease-specific epigenetic-metabolic dysregulation in autoimmune rheumatology.

Disease	Key cellular drivers	Dominant metabolic program	Key epigenetic features	Therapeutic implications	References
RA	FLS, Th17 cells, macrophages	Glycolysis, lactate accumulation	Histone acetylation, EZH2 activation	Target stromal metabolism + epigenetic imprinting	[6, 92–95]
SLE	B cells, pDCs	Glycolysis, glutaminolysis	DNA hypomethylation (ISGs), open chromatin	Target interferon axis + B-cell metabolism	[97–101]
Sjögren’s	Epithelial cells, B cells	Glycolysis, oxidative stress	IFN-response chromatin activation	Target epithelial activation + local immune crosstalk	[103–106]
Systemic sclerosis (SSc)	Fibroblasts	Glycolysis, ROS, lipid dysregulation	Stable profibrotic chromatin states	Target fibroblast reprogramming early	[107–112]

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EZH2: enhancer of zeste homolog 2; FLS: fibroblast-like synoviocytes; IFN: interferon; ISGs: interferon-stimulated genes; pDCs: plasmacytoid dendritic cells; RA: rheumatoid arthritis; ROS: reactive oxygen species; SLE: systemic lupus erythematosus.

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Author contributions

OAA: Conceptualization, Investigation, Visualization, Writing—original draft. MMN: Conceptualization, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing—original draft, Writing—review & editing. Both authors read and approved the submitted version.

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