Recent studies have demonstrated, for instance, that the effect attributed to the two major genetic risk factors for RA (shared epitope of the HLADRB1 and a SNP on the PTPN22 gene) is clearly dependent on the ACPA status having a more evident effect in ACPA-positive subjects than in those lacking of these antibodies38. The gene discussed is PTPN22; the disease is rheumatoid arthritis.