Current Insights into the Pathogenesis of Graves' Ophthalmopathy

R. S. Bahn

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Environmental, genetic, and immune factors are at play in the development of the variable clinical manifestations of Graves' ophthalmopathy (GO). Among the environmental contributions, smoking is the risk factor most consistently linked to the development or worsening of the disease. The close temporal relationship between the diagnoses of Graves' hyperthyroidism and GO have long suggested that these 2 autoimmune conditions may share pathophysiologic features. The finding that the thyrotropin receptor (TSHR) is expressed in orbital fibroblasts, the target cells in GO, supported the notion of a common autoantigen. Both cellular and humeral immunity directed against TSHR expressed on orbital fibroblasts likely initiate the disease process. Activation of helper T cells recognizing TSHR peptides and ligation of TSHR by TRAb lead to the secretion of inflammatory cytokines and chemokines, and enhanced hyaluronic acid (HA) production and adipogenesis. The resulting connective tissue remodeling results in varying degrees extraocular muscle enlargement and orbital fat expansion. A subset of orbital fibroblasts express CD34, are bone-marrow derived, and circulate as fibrocytes that infiltrate connective tissues at sites of injury or inflammation. As these express high levels of TSHR and are capable of producing copious cytokines and chemokines, they may represent an orbital fibroblast population that plays a central role in GO development. In addition to TSHR, orbital fibroblasts from patients with GO express high levels of IGF-1R. Recent studies suggest that these receptors engage in cross-talk induced by TSHR ligation to synergistically enhance TSHR signaling, HA production, and the secretion of inflammatory mediators.

Original languageEnglish (US)
Pages (from-to)773-778
Number of pages6
JournalHormone and Metabolic Research
Volume47
Issue number10
DOIs
StatePublished - Sep 14 2015

Fingerprint

Graves Ophthalmopathy
Fibroblasts
Hyaluronic Acid
Chemokines
Connective Tissue
Ligation
Oculomotor Muscles
Tissue
Cytokines
Thyrotropin Receptors
Adipogenesis
T-cells
Autoantigens
Immunologic Factors
Hyperthyroidism
Helper-Inducer T-Lymphocytes
Cellular Immunity
Muscle
Bone
Bone Marrow

Keywords

  • Graves' disease
  • IGF-1
  • thyroid stimulating hormone
  • TSH-receptor antibodies

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Current Insights into the Pathogenesis of Graves' Ophthalmopathy. / Bahn, R. S.

In: Hormone and Metabolic Research, Vol. 47, No. 10, 14.09.2015, p. 773-778.

Research output: Contribution to journalArticle

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