Effects Of Ultraviolet B Exposure On DNA Methylation Of Peripheral Blood Mononuclear Cells From Systemic Lupus Erythematosus Patients

Objective: To investigate the effects of ultraviolet B on DNA methylation in systemic lupus erythematosus (SLE) patients and its significance in the pathogenesis of SLE.Methods: The study was performed in 45 patients with SLE, 40 females and 5 males. Twenty healthy volunteers, sex- and age- matched, served as a control group. SLE patients met at least 4 of revised criteria of the American College of Rheumatology (ACR). SLE activity was assessed by the SLE disease activity index (SLEDAI), and twenty-four patients with SLEDAI≥10 were considered to have active disease. Peripheral blood mononuclear cells (PBMC) were isolated, and then irradiated by 311 nm narrow band-ultraviolet ray (NB-UVB) at dosages of 50 mJ/cm2, 100 mJ/cm2. DNA methylation was detected by high-performance capillary electrophoresis (HPCE) and DNA methyltransferase 1 (DNMT1) mRNA expression was measured by real-time quantitative PCR (qPCR.). At last, we analyze the correlation between the level of DNA methylation and immunologic and clinical data.Results: The level of DNA methylation in SLE patients was lower than that in control group (P =0.003). DNA methylation was decreased after irradiation at dosages of 50 mJ/cm2, 100 mJ/cm2 (P <0.01), DNA methylation decreased significantly after 50 mJ/cm2 irradiation in active SLE group, while decreased significantly after 100 mJ/cm2 irridation in stable SLE group and control group. Overall, levels of DNA methylation in patients with active SLE were more sensitive to UVB irradiation. No significant difference was observed in DNMT1 mRNA expression after UVB radiation in SLE patients and control group. The DNA methylation levels in untreated SLE patients with glucocorticoids were significantly decreased when compared with that in patients treated with glucocorticoids (P =0.01). SLE patients with facial rash, leukopenia had lower level of DNA methylation (P <0.05). No significant correlation was found between the level of DNA methylation and SLE active index (SLEDAI), various autoantibodies, Immunoglobulins, C3 and C4.Conclusion: UVB exposure plays a pivotal role in the pathogenesis of SLE, which is possibily through inhibition of DNA methylation.