PTPN22 and type 1 diabetes mellitus: The first associations between rs2476601 SNP of PTPN22 gene and autoimmune diseases were demonstrated with type 1 diabetes (T1D) (19) and rheumatoid arthritis (RA) (20); after that, the finding expanded to other autoimmune diseases, enhancing the importance of signaling thresholds in disease susceptibility; even if it is difficult to determine how threshold effects change disease risk.