Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Suedring 10, D-13353 Berlin, Germany.
J Clin Endocrinol Metab. 2013 Feb;98(2):752-60. doi: 10.1210/jc.2012-1771. Epub 2012 Dec 21.
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).
We tested for autoantibodies against the IGF1R (IGF1R-Abs) in sera of GD patients and controls and elucidated their possible implication in the disease.
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.
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.
Our data demonstrate the existence of IGF1R-Abs in humans but do not support the hypothesis that the IGF1R-Abs contribute to GO pathogenesis.
格雷夫斯病（GD）是由针对 TSH 受体的刺激抗体维持的。格雷夫斯眼病（GO）是 GD 的主要甲状腺外表现，可能涉及针对 IGF1 受体（IGF1R）的自身免疫。
我们检测了 GD 患者和对照组血清中的 IGF1 受体自身抗体（IGF1R-Abs），并阐明了它们在疾病中的可能作用。
使用重组人 IGF1R 作为自身抗原建立了 IGF1R-Ab 的诊断检测方法。分析血清样本或纯化的 Ig 制剂在体外对 IGF1R 的结合和 IGF1 信号转导的调节作用。共分析了 108 例连续的 GO 患者，每位患者平均有 5.4 个单独的血清样本，以及 92 名健康对照者。
在 10 名对照者（11%）和 60 名 GO 患者血清库样本（10%）中检测到 IGF1R-Ab。阳性患者样本来自 15 个人，GO 患者的 IGF1R-Ab 患病率为 14%。15 名阳性 GO 患者中有 11 名提供了超过三个连续的样本，平均疾病持续时间为 2 年。这些患者的 IGF1R-Ab 浓度持续升高，表明 IGF1R-Ab 表达随时间相对稳定。IGF1R-Ab 未能刺激 IGF1R 自身磷酸化，但能抑制肝癌 HepG2 细胞中 IGF1 诱导的信号转导。同样，IGF1R-Ab 抑制 MCF7 乳腺癌细胞的生长，支持它们被分类为 IGF1 拮抗剂。
我们的数据表明 IGF1R-Ab 存在于人类中，但不支持 IGF1R-Ab 有助于 GO 发病机制的假说。
