ArticleMolecular biology reports2026
Differential methylation of immune-related genes and its clinical significance in systemic lupus erythematosus: insights from TET2, FOXP3, and IFI44L genes.
Article in Molecular biology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with challenging early diagnosis and effective monitoring due to the limited performance of current biomarkers. Recent research suggests that epigenetic dysregulation, specifically DNA methylation changes in immune-related genes like TET2, FOXP3, and IFI44L, plays a significant role in SLE development and could offer new biomarkers for enhanced diagnosis and comprehensive disease monitoring.
methodsA total of 102 patients with SLE and 105 healthy controls were enrolled in this study. Following the isolation of PBMCs, the promoter methylation levels of TET2, FOXP3, and IFI44L were quantified using the methylation-quantification of endonuclease-resistant DNA (MethyQESD) method. The methylation data were subsequently analyzed to assess diagnostic performance and associations with clinical characteristics.
resultsPromoter methylation of IFI44L was significantly lower in SLE patients compared to healthy controls (P < 0.001) and demonstrated good diagnostic performance (sensitivity = 86.3%, specificity = 74.3%, AUC = 0.847). However, methylation levels of FOXP3 and TET2 did not show significant differences between the two groups. Besides, higher FOXP3 methylation was observed in early-onset SLE patients and those with renal involvement, characterized by positive correlations with CRP and anti-dsDNA antibodies, and negative correlations with complement C3 and C4 levels. TET2 methylation was shown to be elevated in early-onset patients and positively correlated with ESR and anti-dsDNA levels (P < 0.05).
conclusionPromoter methylation of IFI44L, FOXP3, and TET2 plays critical roles in SLE pathogenesis. IFI44L hypomethylation may serve as a diagnostic biomarker, while methylation of FOXP3 and TET2 reflects disease activity, early-onset disease, and renal involvement.
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