Moreover, starting from the results observed in this study, a future perspective which certainly might improve the impact of CTLA4-Ig treatment should be to investigate the capability of CTLA4-Ig to induce the shift from M1 to M2 phenotype in macrophages isolated from RA patients resistant to a previous therapy with anti-TNF drugs as well as in macrophages isolated from patients characterised by genetic variability in CTLA4 (such as those with a single nucleotide polymorphism CTLA-4 rs231775) that was recently demonstrated to decrease the risk of RA [67]. This evidence concerns the gene CTLA4 and rheumatoid arthritis.