This was also taking into consideration the biological relevance of these candidates to RA, as we previously reported on changes in expression of IFITM1 (hypo-methylated and over-expressed) and IRF8 (hyper-methylated and under-expressed) in CD4+ T-cells in early RA compared to HC [39] (Supplementary File), while for TNF-α, changes were observed but were more limited (hypo-methylated but non-significantly over-expressed). This evidence concerns the gene IRF8 and rheumatoid arthritis.