Epigentics in Pulmonary Sarcoidosis Inflammatoy Phenotype

<bold>Aim:</bold> Epigenetic modifications are emerging as important in regulating immune and fibrotic processes through gene expression in lung disease. We aim to assess how this can be applied to sarcoidosis. <bold>Methods:</bold> 79 patents with sarcoidosis underwent methylation analysis of 100ng of genomic DNA extracted from peripheral white blood cells, analysis was carried out using the methylkit package in R. <bold>Results:</bold> We stratified patients by detection of systemic inflammation (ESR >20 or CRP >7) at time of blood draw. 67 patients had no inflammatory signal. We identified 120 targets with q value > 0.05, focusing on genes which had > 5 log2 fold or < -5 Log2 fold change. <fig><object-id>erj;66/suppl_69/PA5133/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> The following genes were identified as differentially methylated in inflammation. <table-wrap><object-id>erj;66/suppl_69/PA5133/TB1</object-id><object-id>T1</object-id><object-id>TB1</object-id><table><colgroup><col></col><col></col></colgroup><tbody><tr><td>Increased methylation in inflammation (reduced gene expression)</td><td>Decreased methylation in inflammation (increased gene expression)</td></tr><tr><td>ADRA2A</td><td>PTPN</td></tr><tr><td>APC2</td><td>SFRP1</td></tr><tr><td>GHSR</td><td>SMDC2</td></tr><tr><td>ITGBL1</td><td>ADAMTS17</td></tr><tr><td>SHH</td><td>DUOXA1</td></tr><tr><td>PAX1</td><td>SLC19A1</td></tr><tr><td>PPL</td><td>SHISAL1</td></tr><tr><td></td><td>CPNE2</td></tr></tbody></table></table-wrap> Conslusion Pathway analysis indicated genes with reduced activity were involved in a range of functions related to Sarcoidosis including adaptive immunity, interferon signalling, cell migration, and regulation T cell immunity. Genes with increased activity were involved in Interleukin signalling, and neutrophil degranulation. These genes have functions directly linked to the immune system, tissue remodelling, inflammation, or cell signalling, all of which are central in the pathophysiology of sarcoidosis.