title: Circulating IgGs may modulate IGF-I receptor stimulating activity in a subset of patients with Graves' ophthalmopathy.
abstract: BACKGROUND
  There is a close association between levels of TSH binding inhibitory immunoglobulins (TBIIs) and Graves' ophthalmopathy (GO). In addition to the TSH receptor, the IGF-I receptor (IGF-IR) has been proposed to be a second autoantigen that plays a role in the pathogenesis of GO.
  
  
  OBJECTIVE
  The aim was to study relationships between TBII and serum IGF-IR stimulating activity in relationship to age in patients with GO.
  
  
  METHODS
  We performed a prospective study of 70 patients with GO (26 euthyroid, 39 subclinical hyperthyroid, 5 hyperthyroid; 8 males, 62 females; age, 47.9 ± 1.0 y). Patients were graded according to clinical activity score. IGF-IR stimulating activity was determined by IGF-IR kinase receptor activation assay; TBIIs were measured by immunoassay (Trak). Protein G magnetic beads were used to deplete serum of IgGs.
  
  
  RESULTS
  TBII and clinical activity score were positively related (r = 0.30; P = .01). In subjects with TBII above mean +1 SD, IGF-IR stimulating activity was positively related to age (r = 0.43; P = .05), whereas such a relationship was absent for subjects with TBII below the mean +1 SD (r = -0.04; P = .81). Depletion of IgGs from sera of patients with both TBII above the mean +1 SD and IGF-IR stimulating activity above the mean -1 SD decreased IGF-IR stimulating activity, whereas depletion in patients with TBII above the mean +1 SD but IGF-IR stimulating activity below the mean -1 SD did not change IGF-IR stimulating activity.
  
  
  CONCLUSIONS
  In subjects with TBII above the mean +1 SD, we observed an increase of IGF-IR stimulating activity with age. In a subgroup of these patients, depletion of IgGs significantly decreased IGF-IR stimulating activity, suggesting that, in a subset of patients with GO, IgGs may have IGF-IR stimulating activities.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Aimee J
authors.initials: AJ
authors.lastname: Varewijck
authors.forename: Anita
authors.initials: A
authors.lastname: Boelen
authors.forename: Steven W J
authors.initials: SW
authors.lastname: Lamberts
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: Wilmar M
authors.initials: WM
authors.lastname: Wiersinga
authors.forename: Joseph A M J L
authors.initials: JA
authors.lastname: Janssen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D049970:Graves Ophthalmopathy / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011989:Receptors, Thyrotropin / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin; D017526:Receptor, IGF Type 1