DNA methylation in SLE-related autoantibodies

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can have debilitating effects on multiple organ systems. In SLE, the pivotal immunologic disturbance is the formation of autoantibodies directed against nuclear and cellular antigens. These autoantibodies are associated with specific organ manifestations. Our previous work has shown that certain single nucleotide polymorphisms (SNPs) are associated with the production of SLE-related autoantibodies. However, these genetic associations do not completely explain autoantibody development in SLE. Therefore, we examined whether epigenetic factors such as DNA methylation may be associated with the development of SLE-related autoantibodies. In this study, we examined whether differential DNA methylation is associated with anti-dsDNA, anti-SSA/Ro, anti-Smith, and anti-RNP autoantibodies. Using the Illumina HumanMethylation450 Beadchip, over 450,000 DNA methylation sites were characterized in 325 female SLE cases of European descent. Using a multivariable regression analyses, the methylation status of 16 CpG sites in 11 genes was found to be associated with the SLE-related autoantibodies under study. This study shows that epigenetic factors are associated with autoimmune disease phenotypes, and epigenetic studies are a complementary method to genetic association studies for understanding the biologic mechanisms contributing to autoimmune disease.]]>
This study included women of European descent who met the American College of Rheumatology (ACR) criteria for a diagnosis of SLE as determined by medical record review. The women included in the study reported no history of smoking through questionnaires.]]>
Participants in the Genome-wide assessment of DNA methylation in SLE-related autoantibodies study are part of the Lupus Genetics Research Project at the University of California, San Francisco (UCSF). For the Lupus Genetics Research Project, lupus patients were recruited nationwide and through rheumatology clinics at UCSF and rheumatology practices in the San Francisco area. Participants in the Lupus Genetics Project have been studied in candidate gene and genome-wide association studies of SLE.]]>