Furthermore, aetiology and pathogenesis of RA have not been completely elucidated, but it is widely accepted that is a multifactorial disease associated with genetic factors (HLA genes, as HLA-DRw4 and HLA-DRB1, PTPN22 (encoding tyrosine-protein phosphatase non-receptor type 22) gene, protein-arginine deiminase type 4 (PADI4) gene and cytotoxic T-lymphocyte protein 4 (CTLA-4) gene), environmental (e.g., cigarette smoke), gender and age [148–150]. Here, CTLA4 is linked to rheumatoid arthritis.