Differential CpG methylation of the promoter of interleukin 8 and the first intron of tissue factor in Antiphospholipid syndrome.

摘要: Abstract Background Antiphospholipid syndrome (APS) is an autoimmune thrombophilia characterized by recurrent thromboembolism and/or pregnancy morbidity in the presence of antibodies, mainly anti-β2 glycoprotein I (anti-β2GPI). The autoantibodies lead to monocyte and endothelial cell activation subsequent secretion tissue factor (F3) proinflammatory cytokines, like interleukins 6 (IL6) 8 (IL8). etiology remains largely unknown, with contribution environmental, genetic epigenetic factors considered significant. Purpose We aimed identify changes potentially implicated pathophysiology APS. To this end, we compared DNA methylation levels IL8 F3 genes between healthy donors (HDs) APS patients, using whole blood as a source. Results Methylation was significantly reduced promoter increased gene body patients HDs correlated specific clinical parameters. In ex vivo model partially mimicking APS, stimulation monocytes mixture β2GPI, anti-β2GPI CXCL4 also induces above genes, along increase their expression. Stimulation human umbilical vein cells (HUVECs) same results transcriptional upregulation factors, including MECP2, DNMT3, TET1, HDAC9 ARID5B. Conclusions data support that alterations could be prompt further investigation potential diagnostic or therapeutic utility.