Diagnostic and clinical implications of PARP9 promoter methylation in systemic lupus erythematosus and rheumatoid arthritis.

ObjectiveAccurate diagnosis and continuous monitoring are crucial for effective management of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Conventional biomarkers exhibit limitations regarding their sensitivity and specificity. Recent research highlights the importance of DNA methylation, particularly in the PARP9 gene, in relation to these diseases. This study examines PARP9 promoter methylation in peripheral blood mononuclear cells (PBMCs) obtained from SLE and RA patients to evaluate its diagnostic potential.MethodsIn this study, we assessed the quantitative methylation levels of the PARP9 promoter in PBMCs from 75 SLE patients, 75 RA patients, and an equal number of healthy controls using methylation-quantification of endonuclease-resistant DNA (MethyQESD) method.ResultsThe study revealed significant hypomethylation of the PARP9 promoter in both SLE and RA patients compared to control group (p < .001). The optimal cutoff values identified were 24.31% for SLE, demonstrating a sensitivity of 81.33%, and a specificity of 77.33%, and 27.73% for RA patients with a sensitivity of 77.33%, and a specificity of 70.66%). ROC curve analysis showed an AUC of 0.758 for SLE and 0.717 for RA, reflecting a moderate diagnostic accuracy (p < .001). Additionally, hypomethylation of PARP9 was negatively correlated with anti-dsDNA levels in SLE patients and with ESR and CRP levels in RA patients, while showed a positive correlation with C3 and C4 levels in SLE group (p < .001).ConclusionPARP9 promoter hypomethylation shows potential as a diagnostic biomarker for SLE and RA. The significant association between hypomethylation of PAPR9 promoter and disease activity factors in SLE and RA patients, is suggesting that PARP9 hypomethylation could be used as an alternative biomarker for monitoring of disease activity.