Stages of an autoimmune disease

What are the stages of an autoimmune disease?

Autoimmune diseases generally follow three stages:

1. Genetic risk: some genes contribute significant risk (e.g., HLA), whereas most genes (e.g., PTPN22, STAT4) confer a modest risk (usually 2–3 fold), but in aggregate, the risk is quite high in the setting of a combination of disease-promoting polymorphisms, which are usually (90%) in regulatory proteins and the “right” environmental exposure. Epigenetics (DNA methylation, histone modifications, microRNAs) also contribute to the genetic predisposition.

2. Autoimmunity: the development of autoimmune phenomena such as autoantibodies produced by B cells that have lost self-tolerance (and presumably driven by autoimmune T cells) but in a state wherein the individual still does not exhibit symptoms because the target organs have not yet become damaged to a sufficient level.

3. Disease: the third stage is the development of clinical symptoms that impair quality of life and require treatment. Although most autoimmune diseases are detected and treated only in the third phase, ongoing work in several diseases is expected to allow the detection of a “preclinical” disease state in which specific preventive therapies could be used.

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