Multistep pathogenesis of autoimmune disease

Cell. 2007 Jul 13;130(1):25-35. doi: 10.1016/j.cell.2007.06.033.


In the immune system, many tolerance checkpoints exist to prevent self-antigens from stimulating the relentless growth of self-reactive B and T lymphocytes. The genes and molecular pathways underpinning these checkpoints overlap with those involved in tumor suppression. As with an inherited predisposition to cancer, inherited defects in self-tolerance genes typically precipitate autoimmune disease stochastically after a latent phase. Multiple mutations, inherited and somatic, may be needed before a self-reactive clone bypasses sequential tolerance checkpoints resulting in the emergence of autoimmune disease.

Publication types

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

MeSH terms

  • Animals
  • Antigens / immunology
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / physiopathology*
  • Autoimmunity / genetics
  • Autoimmunity / physiology*
  • Biological Evolution
  • Humans
  • Immune System / physiology*
  • Immune Tolerance / genetics
  • Immune Tolerance / physiology*
  • Lymphocytes / physiology
  • Lymphoma / genetics
  • Lymphoma / immunology
  • Mutation
  • Signal Transduction / physiology


  • Antigens