In this regard, enhanced production of activin A could be observed after stimulation of monocytes derived from human peripheral blood with synovial fluid of RA patients and macrophages from the synovial fluid of RA patients showed a higher expression of p-R-Smad2 in comparison to pro-inflammatory or anti-inflammatory macrophages derived from peripheral blood mononuclear cells [91]. This evidence concerns the gene SMAD2 and rheumatoid arthritis.