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Autoimmune thyroid disease: unlocking a complex puzzle

2009; Lippincott Williams & Wilkins; Volume: 21; Issue: 4 Linguagem: Inglês

10.1097/mop.0b013e32832cf824

1531-698X

Rosalind S. Brown,

T-cell and B-cell Immunology

The autoimmune thyroid diseases (AITD), Graves' disease and chronic lymphocytic thyroiditis (CLT) are amongst the most common endocrine diseases in childhood and adolescence. The application of molecular biology has permitted an unparalleled insight into susceptibility genes that predispose to their development and has allowed enhanced understanding of their complex immune pathophysiology.The susceptibility genes that predispose to AITD can be subdivided into those that affect the immune response in general and thyroid-specific antigens. Both known and new susceptibility genes have been the focus of recent attention. Although there is no known human leukocyte antigen (HLA) association in CLT, recent work has demonstrated an association with a specific amino acid pocket signature irrespective of the HLA-DR class. In Graves' disease a specific combination of polymorphisms for thyroglobulin and HLA-DR markedly increases the odds ratio for developing disease. The availability of recombinant antigen [particularly thyroid peroxidase and thyrotropin (TSH) receptor] and of high affinity monoclonal antibodies has provided insight into the specific epitopes recognized by antibodies in AITD and has confirmed the increased affinity of stimulating TSH receptor antibodies for the shed A subunit rather than the holoreceptor.Powerful molecular tools have been developed that have shed light on the nature of the susceptibility genes for and the pathophysiology of AITD. These have already led to improved diagnostic tools and, hopefully, will permit the development of more specific immune therapy in the future.