Article

Autoantibodies to the IGF1 Receptor in Graves' Orbitopathy

Institute for Experimental Endocrinology (W.B.M., N.D., T.W., C.S., N.G.M., J.K., L.S.), Charité-Universitätsmedizin Berlin, D-13353 Berlin, Germany
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.31). 12/2012; 98(2). DOI: 10.1210/jc.2012-1771
Source: PubMed

ABSTRACT Context: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.Design: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.

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