The HLA gene complex in thyroid autoimmunity: From epidemiology to etiology

Eric M. Jacobson, Amanda Huber, Yaron Tomer

Research output: Contribution to journalReview articlepeer-review

195 Scopus citations


The autoimmune thyroid diseases (AITD) comprise a cadre of complex diseases whose underlying pathoetiology stems from a genetic-environmental interaction, between susceptibility genes (e.g. CTLA-4, HLA-DR, thyroglobulin) and environmental triggers (e.g. dietary iodine), that orchestrates the initiation of an autoimmune response to thyroid antigens, leading to the onset of disease. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Several AITD susceptibility genes have been identified, with HLA genes, in particular, appearing to be of major importance. Early studies showed association of HLA-DR3 with Graves' disease (GD) in Caucasians. More recently, the importance of an amino acid substitution at position 74 of the DR beta 1 chain of HLA-DR3 (DRb1-Arg74), in susceptibility to Graves' disease, has been shown. Furthermore, there is increasing evidence for a genetic interaction between thyroglobulin variants and DRb1-Arg74 in conferring risk for GD. Mechanistically, the presence of an arginine at position 74 elicits a significant structural change in the peptide binding pocket of HLA-DR, potentially affecting the binding of pathogenic thyroidal peptides. Future therapeutic interventions may attempt to exploit this new bolus of knowledge by endeavoring to block or modulate pathogenic peptide presentation by HLA-DR.

Original languageEnglish (US)
Pages (from-to)58-62
Number of pages5
JournalJournal of Autoimmunity
Issue number1-2
StatePublished - Feb 2008
Externally publishedYes


  • Association
  • Gene
  • Graves' disease
  • HLA
  • Hashimoto's thyroiditis
  • Linkage
  • Thyroid

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'The HLA gene complex in thyroid autoimmunity: From epidemiology to etiology'. Together they form a unique fingerprint.

Cite this