Through binding to surface, over-expressed, citrullinated glucose-regulated protein 78 on RA peripheral blood mononuclear cells, ACPAs selectively activate the ERK1/2 and JNK signaling pathways to enhance IKK-α phosphorylation, which leads to the activation of NF-κB and the production of TNF-α [79]. This evidence concerns the gene TNF and rheumatoid arthritis.