Abstract
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thromboembolic events and pregnancy loss. We sought to characterize the DNA methylation profile of primary APS in comparison to healthy controls and individuals with SLE. In primary APS neutrophils compared to controls, 17 hypomethylated and 25 hypermethylated CpG sites were identified. Notable hypomethylated genes included ETS1, a genetic risk locus for SLE, and PTPN2, a genetic risk locus for other autoimmune diseases. Gene ontology analysis of hypomethylated genes revealed enrichment of genes involved in pregnancy. None of the differentially methylated sites in primary APS were differentially methylated in SLE neutrophils, and there was no demethylation of interferon signature genes in primary APS as is seen in SLE. Hypomethylation within a single probe in the IFI44L promoter (cg06872964) was able to distinguish SLE from primary APS with a sensitivity of 93.3% and specificity of 80.0% at a methylation fraction of 0.329.