A CD4+ T cell-driven disease is further supported by the clinical effectiveness of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)Ig that blocks Th cell co-stimulation in untreated early RA (eRA) patients [4,5], and its inhibitory effect on RA development in individuals at high risk [6,7]. This evidence concerns the gene CD4 and rheumatoid arthritis.