Circulating IgGs May Modulate IGF-I Receptor Stimulating Activity in a Subset of Patients With Graves' Ophthalmopathy

Abstract

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. The aim was to study relationships between TBII and serum IGF-IR stimulating activity in relationship to age in patients with GO. 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. 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. 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.