In addition, genetic differences between ACPA-positive and ACPA-negative RA have been demonstrated, e.g., variants in HLA-DRB1, PTPN22, BLK, Ankyrin Repeat Domain 55 (ANKRD55), and IL6ST are associated with RA regardless of serological status, whereas AFF3, CD28, and TNFAIP3 are found only in seropositive RA, and PRL and NFIA are found only in seronegative RA [46,47]. This evidence concerns the gene PTPN22 and rheumatoid arthritis.