DNA methylation of human endogenous retrovirus in systemic lupus erythematosus

Abstract

Previous studies have reported that T cells from active systemic lupus erythematosus (SLE) patients contained global hypomethylation and demethylation at the promoter of several genes, which may contribute to the pathogenesis of the disease. Currently there are scarce data on methylation of retroelements in patients with SLE. We estimated and compared the methylated levels of human endogenous retroviruses (HERV)-E and HERV-K in normal and SLE CD3+CD4+ T lymphocytes, CD8+ T and B lymphocytes by using combined bisulfite restriction analysis-interspersed repetitive sequences (COBRA-IRS). HERV-E LTR2C methylation level in CD3+CD4+ T lymphocytes of active SLE was significantly lower than inactive SLE and normal controls (P=0.023 and 0.035, respectively). Surprisingly, HERV-K LTR5-Hs hypomethylation was significantly detected in CD3+CD4+ T lymphocytes from patients with inactive SLE when compared with the active SLE and normal controls (P=0.027 and 0.002, respectively). Demethylation of HERV-K LTR5-Hs in B cells was also detected when compared with the normal controls (P=0.048). Furthermore, the hypomethylation of HERV-E LTR2C in CD3+CD4+ T lymphocytes was positively correlated with lymphopenia in active SLE, whereas the hypomethylation of HERV-K LTR5-Hs was significantly correlated with complement activity and Systemic Lupus Erythematosus Disease Activity Index score. In summary, for each lymphocyte subset in patients with SLE, IRS hypomethylation was found to be type specific. Further studies are needed to confirm and explain these observations. © 2013 The Japan Society of Human Genetics All rights reserved.