title: Autoantibodies to the IGF1 receptor in Graves' orbitopathy.
abstract: BACKGROUND
  Graves' disease (GD) is maintained by stimulating antibodies against the TSH receptor. Graves' orbitopathy (GO) is the main extrathyroidal manifestation of GD, potentially involving autoimmunity against the IGF1 receptor (IGF1R).
  
  
  OBJECTIVE
  We tested for autoantibodies against the IGF1R (IGF1R-Abs) in sera of GD patients and controls and elucidated their possible implication in the disease.
  
  
  METHODS
  A diagnostic assay for IGF1R-Ab was established with recombinant human IGF1R as autoantigen. Serum samples or purified Ig preparations were analyzed for IGF1R binding and modulation of IGF1 signaling in vitro. A total of 108 consecutive GO patients represented on average by 5.4 separate serum samples per individual along with 92 healthy controls were analyzed.
  
  
  RESULTS
  IGF1R-Ab were detected in 10 serum samples from control subjects (11%) and in 60 samples (10%) from the GO patient serum bank. The positive patient samples were derived from 15 individuals yielding an IGF1R-Ab prevalence of 14% in GO. More than three consecutive samples were available from 11 of the 15 positive GO patients spanning an average disease period of 2 years. IGF1R-Ab concentrations were constantly elevated in these patients demonstrating relatively stable IGF1R-Ab expression over time. IGF1R-Ab failed to stimulate IGF1R autophosphorylation but instead inhibited IGF1-induced signaling in hepatocarcinoma HepG2 cells. Similarly, growth of MCF7 breast cancer cells was inhibited by IGF1R-Ab, supporting their classification as IGF1 antagonists.
  
  
  CONCLUSIONS
  Our data demonstrate the existence of IGF1R-Abs in humans but do not support the hypothesis that the IGF1R-Abs contribute to GO pathogenesis.
authors.affiliation: Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Suedring 10, D-13353 Berlin, Germany.
authors.forename: Waldemar B
authors.initials: WB
authors.lastname: Minich
authors.forename: Nora
authors.initials: N
authors.lastname: Dehina
authors.forename: Tim
authors.initials: T
authors.lastname: Welsink
authors.forename: Christian
authors.initials: C
authors.lastname: Schwiebert
authors.forename: Nils G
authors.initials: NG
authors.lastname: Morgenthaler
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.forename: Anja
authors.initials: A
authors.lastname: Eckstein
authors.forename: Lutz
authors.initials: L
authors.lastname: Schomburg
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D005260:Female; D049970:Graves Ophthalmopathy / Q000097:blood / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D017526:Receptor, IGF Type 1