Meanwhile, the PADI4 risk allele was associated with bone damage regardless of ACPA positivity in Asian RA patients.127 ACPA binds citrullinated residues on many of the body’s own proteins, including histones, vimentin, fibronectin, fibrinogen, type II collagen, and alpha-enolase, the activated immune responses tissue is uncertain.128 Circulated ACPAs could be detected up to 10 years before diagnosis known as pre-RA.129–133 As time progresses, the epitope diversity and concentration of ACPAs increase, and so do the concentrations of serum cytokine. This evidence concerns the gene PRTN3 and rheumatoid arthritis.