FRI0284 Altered patterns of histone acetylation point to mechanisms of transcriptional dysregulation in patients with systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease designated by a heterogeneous course and systemic nature. It arises as a result of complex pathways, as well as the interaction of genetic and environmental factors, leading to the altered reactivity of the immune system that culminates in autoantibody formation. Epidemiological studies have shown an important role of the genetic component in the emergence of SLE and genome-wide association studies have identified more than 50 SLE-associated risk loci, pointing to a complex genetic background. Objectives The aim of the study was to further elucidate the genetic mechanisms influencing the development of SLE. Methods We performed chromatin immunoprecipitation experiments to ascertain the levels of histone acetylation in peripheral blood mononuclear cells collected from 5 recent onset and treatment naive SLE patients compared to 5 age and gender matched controls. Results The analysis revealed 16 379 significantly enriched genomic regions in control patients compared to 39 204 significantly enriched genomic regions in SLE patients. Among the SLE specific regions several pathways were significantly enriched including the adaptive immune system pathway, cytokine signalling in immune system, disease of immune system and inflammation mediated by chemokine and cytokine pathway. Conclusions The collective data point to a significant alteration of histone acetylation patterns in SLE patients possibly mediated by the DNA specific autoantibodies. The results of the study offer additional insight into the genetics of SLE pointing to putative mechanisms of transcriptional dysregulation. Disclosure of Interest None declared