PTPN22: setting thresholds for autoimmunity

Semin Immunol. 2006 Aug;18(4):214-23. doi: 10.1016/j.smim.2006.03.009. Epub 2006 May 30.


The 620W allelic variant of the intracellular tyrosine phosphatase, PTPN22, is associated with a number of different autoimmune disorders, and this provides direct evidence for common mechanisms underlying many of these diseases. The associated allele appears to influence thresholds for T cell receptor signaling, and a variety of disease models involving both central and peripheral tolerance can be proposed. However, given the fact that PTPN22 is expressed in a variety of immunologically relevant cell types, the precise mechanisms for these associations remain unclear. In general, the PTPN22 620W allele appears to play a role in autoimmune disorders that have a prominent humoral component, suggesting that further investigation of PTPN22 activity in B cells will be useful. From a genetic perspective, the data highlights the genetic heterogeneity underlying autoimmunity in different ethnic groups.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Animals
  • Autoimmune Diseases / enzymology*
  • Autoimmune Diseases / ethnology
  • Autoimmune Diseases / genetics
  • Genetic Variation
  • Humans
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22
  • Protein Tyrosine Phosphatases / genetics*
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction
  • T-Lymphocytes / immunology


  • Receptors, Antigen, T-Cell
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22
  • Protein Tyrosine Phosphatases