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

Eric M. Jacobson, Amanda Huber, Yaron Tomer

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

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
Volume30
Issue number1-2
DOIs
StatePublished - Feb 2008
Externally publishedYes

Fingerprint

Graves Disease
Thyroid Diseases
HLA-DR Antigens
Autoimmunity
HLA-DR3 Antigen
Autoimmune Diseases
Thyroid Gland
Epidemiology
Thyroglobulin
Peptides
Genes
Twin Studies
Disease Susceptibility
Amino Acid Substitution
Iodine
Arginine
Antigens
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

The HLA gene complex in thyroid autoimmunity : From epidemiology to etiology. / Jacobson, Eric M.; Huber, Amanda; Tomer, Yaron.

In: Journal of Autoimmunity, Vol. 30, No. 1-2, 02.2008, p. 58-62.

Research output: Contribution to journalArticle

Jacobson, Eric M. ; Huber, Amanda ; Tomer, Yaron. / The HLA gene complex in thyroid autoimmunity : From epidemiology to etiology. In: Journal of Autoimmunity. 2008 ; Vol. 30, No. 1-2. pp. 58-62.
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