title: The pathophysiology of thyroid eye disease: implications for immunotherapy.
abstract: OBJECTIVE
  Thyroid eye disease (TED) is a poorly understood autoimmune manifestation most commonly associated with Graves' disease. Current nonspecific treatment paradigms offer symptomatic improvement but fail to target the underlying pathogenic mechanisms, and thus do not significantly alter the long-term disease outcome. The purpose of this review is to provide an update of the current understanding of the immunopathogenesis of TED and explore these mechanisms for targeted immunotherapy.
  
  
  RESULTS
  Orbital fibroblasts are integral to the pathogenesis of TED and may modulate immune responses by production of cytokines and hyaluronan in response to activation of shared autoantigens including thyrotropin receptor and insulin-like growth factor-1 receptor. Bone marrow-derived fibrocytes share many of these phenotypic and functional features, suggesting a link between systemic and site-specific disease. Use of targeted immunotherapies in TED is limited, though data from the use Rituximab (RTX), a B-cell depleting agent, are encouraging. Sustained clinical response has been seen with RTX in several reports, despite return of peripheral B-cell levels to pretreatment levels. Additionally, this response appears to be independent of cytokine and antibody production, suggesting modulation of antigen presentation as a mechanism of its effect.
  
  
  CONCLUSIONS
  Progressive advances in the understanding of the immunopathogenesis of TED continue to spur clinical trials utilizing targeted immune therapies. Continued understanding of the molecular mechanisms of disease will expand potential treatments for TED patients and obviate the need for reconstructive surgical therapies.
authors: Thyroid Eye Disease Center at the Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan 48105, USA. raydougl@med.umich.edu
authors: Raymond S
authors: RS
authors: Douglas
authors: Shivani
authors: S
authors: Gupta
mesh_terms: D001324:Autoantigens; D018450:Disease Progression; D005260:Female; D049970:Graves Ophthalmopathy / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D008297:Male; D010641:Phenotype; D011989:Receptors, Thyrotropin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001324:Autoantigens; D011989:Receptors, Thyrotropin