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Cytokine dysregulation is one of the important hallmarks of systemic lupus erythematosus (SLE) in both pediatric and adult patients. Owing to the substantial role of Janus kinase (JAK) and suppressor of cytokine signaling (SOCS) in cytokine signaling, we compared the methylation status of the promoter of JAK2 and SOCS3 between patients with JSLE and healthy controls. Methods:Peripheral blood samples were obtained from patients with JSLE and healthy controls. The promoter methylation was assessed by using the bisulfite conversion system and real-time quantitative multiplex methylation-specific PCR (QM-MSP). Results:The methylation assessments were performed on the blood samples of 25 patients with JSLE and 24 healthy controls. The promoter of JAK2 was significantly hypomethylated in patients with JSLE compared to healthy controls. The median relative unmethylation of the promoter of JAK2 was higher in the JSLE group compared to the control group [0.44 (0.32, 0.59) vs. 0.18 (0.12, 0.86), respectively; P-value 0.026]. The promoter of SOCS3 was significantly hypermethylated in patients with JSLE compared to the controls. The median relative unmethylation of the promoter of SOCS3 was lower in the JSLE group compared to the control group [0.52 (0.10, 1.41) vs 1.18 (0.39, 2.19), respectively ; P-value 0.032]. Conclusion:According to the results of our study, hypomethylation of the promoter of JAK2 and hypermethylation of the promoter of SOCS3 associate with JSLE. These alterations are possible mechanisms for activation of the JAK2 and suppression of the SOCS3 gene, respectively.