PRTN3 and periodontal disorder: This pathway includes smoking and periodontal disease as sources of citrullination of proteins, specific HLA-DRB1 alleles to present citrullinated peptides, and other genetic factors as positive modulators of antibody mediated autoreactivity; epitope spreading together with maturation of the antibody response as steps preceding clinical onset of RA, and the effect of ACPA in stimulating osteoclasts for the RA bone erosions.