It has been previously reported that the HLA-DRB1*13 allele has a dual role: as genetic modulator of ACPA positivity, whereby it was inversely associated with risk of ACPA-positive RA; but also, in combination with HLA-DRB1*03, it decreased the risk of ACPA-negative RA [36]. This evidence concerns the gene HLA-DRB1 and rheumatoid arthritis.