Autoimmune thyroid disease: unlocking a complex puzzle

Curr Opin Pediatr. 2009 Aug;21(4):523-8. doi: 10.1097/MOP.0b013e32832cf824.


Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Animals
  • Antibody Formation
  • Antigens, CD / genetics
  • Apoptosis / immunology
  • CD40 Antigens / genetics
  • CTLA-4 Antigen
  • Child
  • Child, Preschool
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Graves Disease
  • HLA Antigens / genetics
  • Hashimoto Disease / genetics*
  • Hashimoto Disease / immunology*
  • Humans
  • Immunity, Cellular
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Thyroiditis, Autoimmune / genetics*
  • Thyroiditis, Autoimmune / immunology*


  • Antigens, CD
  • CD40 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • HLA Antigens
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22