The study of DNA methylation status of the interspersed repetitive sequences type LINE-1, ALU, HERV-E AND HERV-K in neutrophil of systemic lupus erythematosus patients and healthy controls

Abstract

The exact etiology of Systemic Lupus Erythematosus (SLE) is still obscure. Various report believe that the epigenetic, it important role that may cause SLE. One of the major mechanisms of epigenetic be DNA methylation, it is possible an important cause of the disease. Several papers report that abnormalities of DNA methylation level in some important immune cells and SLE-relate genes of SLE patients. It was found that leukocytes, PBMC, T-cell and CD4+ T-cell DNA of SLE patients are DNA hypomethylation comparing to healthy donor. Not only are PBMC and lymphocyte is those involve with pathogenesis of SLE but have also been neutrophil. Several papers reported that abnormalities in cell-death processes of SLE neutrophils. DNA methylation that involved the addition of a methyl group to cytosine within CpG pairs. That does not only occur in genes but also occur on the IRSs in human genome. Previous studies report that methylation levels of IRSs in PBMC and Lymphocyte of SLE’s patients but limited in Neutrophils. In this study we evaluated methylation level and patterns of LINE-1, ALU, HERV-E and HERV-K in SLE’s patient compared to healthy controls and examined the association between methylation level and patterns according to age and some clinical data of SLE patients. We observed that some methylation level and pattern of LINE-1 was significant difference, precise methylation (mC), hypermethylated (mCmC) in neutrophils from SLE patients were significantly lower than healthy controls. (p-value<0.0001, p-value<0.0001 respectively) and found that hypomethylation (uCuC) and %mCuC pattern in neutrophils from SLE patients were significantly higher than healthy controls. (P-value=0.0028, p-value<0.0001 respectively). However, the methylation level and pattern of Alu, HERV-E and HERV-K in neutrophils from SLE patients include active and inactive group compared to healthy control were not significantly different. Moreover, we investigate the correlation between intragenic LINE-1 and differential expressions in SLE neutrophils expression array. We explored higher prevalence of up-regulated of genes containing LINE-1s (p-value= 7.74X10-3; OR = 1.28). Moreover, genes with antisense LINE-1s were higher prevalence of up-regulated genes containing LINE-1s (p-value= 6.22X10-3; OR = 1.38). We also provided an evidence to propose the dynamics of DNA methylation levels and pattern of LINE-1 in Neutrophils might affect to pathogenesis of the SLE. However, this study is the first evidence that could lead to new knowledge related to the etiology of SLE.