Hypomethylation of LINE-1 but not Alu in lymphocyte subsets of systemic lupus erythematosus patients

Background: T lymphocytes from SLE patients have a global decrease in the 5-methylcytosine content. Previous studies have identified hypomethylation in the promoter of several genes but there is limited study in the interspersed repetitive sequences (IRSs).

Methods: We examined and compared the methylation levels of long interspersed nuclear element 1s (LINE-1) and Alu elements in normal and SLE CD4+ T lymphocytes, CD8+ T lymphocytes and B lymphocytes by the combined bisulfite restriction analysis-interspersed repetitive sequences (COBRA-IRS).

Results: Hypomethylation of LINE-1 but not Alu was found in CD4+ T lymphocytes, CD8+ T lymphocytes, and B lymphocytes of SLE patient (P=0.005, 0.002, and 0.007, respectively). Moreover, when the SLE patients were divided into active and inactive groups, LINE-1 hypomethylation was more significantly distinguished in both CD4+ and CD8+ T lymphocytes of patients from the active SLE group when compared to the controls. Surprisingly, Alu hypomethylation was also observed in CD8+ T lymphocytes from the inactive SLE group when compared to the normal controls (P=0.0056).

Conclusions: The hypomethylation in each lymphocyte subset of SLE was IRSs specific, mainly found in LINE-1 rather than Alu.