Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Rev Endocrinol. 2012 Jan 31;8(5):306-16. doi: 10.1038/nrendo.2011.245.

Autoimmune Addison disease: pathophysiology and genetic complexity.

Author information

1
Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK. anna.mitchell@ ncl.ac.uk

Abstract

Autoimmune Addison disease is a rare autoimmune disorder with symptoms that typically develop over months or years. Following the development of serum autoantibodies to the key steroidogenic enzyme, 21-hydroxylase, patients have a period of compensated or preclinical disease, characterized by elevations in adrenocortocotropic hormone and renin, before overt, symptomatic adrenal failure develops. We propose that local failure of steroidogenesis, causing breakdown of tolerance to adrenal antigens, might be a key factor in disease progression. The etiology of autoimmune Addison disease has a strong genetic component in man, and several dog breeds are also susceptible. Allelic variants of genes encoding molecules of both the adaptive and innate immune systems have now been implicated, with a focus on the immunological synapse and downstream participants in T lymphocyte antigen-receptor signaling. With the exception of MHC alleles, which contribute to susceptibility in both human and canine Addison disease, no major or highly penetrant disease alleles have been found to date. Future research into autoimmune Addison disease, making use of genome-wide association studies and next-generation sequencing technology, will address the gaps in our understanding of the etiology of this disease.

PMID:
22290360
DOI:
10.1038/nrendo.2011.245
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center