It is therefore difficult to compare these data with our findings; also, given the use of a mixed cohort of ACPA+ and/or IgM-FR+ patients with arthralgia, several studies having showed clear reduction of naïve cells and Treg in early RA.28, 30–32 Loss of immune regulation may be an important immunological event in the progression of a disease. This evidence concerns the gene CD40LG and rheumatoid arthritis.