PRTN3 and rheumatoid arthritis: There is increasing evidence of genetic and molecular heterogeneity of RA: for instance, anti-citrullinated protein antibody (ACPA) positive disease is associated with different genetic (e.g. PTPN22) and environmental (e.g. smoking) risk factors when compared to ACPA-negative disease [14], and is associated with a higher rate of radiographic progression [15].