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Cell. 2007 Jul 13;130(1):25-35.

Multistep pathogenesis of autoimmune disease.

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John Curtin School of Medical Research and Australian Phenomics Facility, The Australian National University, Canberra ACT 2601, Australia.


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.

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