Is There Evidence for IGF1R-Stimulating Abs in Graves' Orbitopathy Pathogenesis?

• Published in: International journal of molecular sciences 2020-09, Vol.21 (18), p.6561
• Main Authors: Krieger, Christine C, Neumann, Susanne, Gershengorn, Marvin C
• Format: Article
• Language: English
• Subjects: Antibodies; Antigens; Autoantibodies; Autoantibodies - immunology; Cell growth; Crosstalk; Disease; Drug development; Graves Ophthalmopathy - immunology; Graves Ophthalmopathy - pathology; Graves’ orbitopathy; Growth factors; Humans; Hyaluronic Acid - metabolism; Hyperthyroidism; Hypotheses; IGF1R; IGF1R antibodies; Insulin; Investigations; Kinases; Ligands; Pathogenesis; Receptor Cross-Talk - immunology; receptor crosstalk; Receptor, IGF Type 1 - immunology; Receptor, IGF Type 1 - metabolism; Receptors, Somatomedin; Receptors, Thyrotropin - immunology; Receptors, Thyrotropin - metabolism; Review; Thyroid; Thyroid gland; Thyroid-stimulating hormone; Thyroid-stimulating hormone receptors; TSHR; TSHR antibodies
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21186561

In this review, we summarize the evidence against direct stimulation of insulin-like growth factor 1 receptors (IGF1Rs) by autoantibodies in Graves' orbitopathy (GO) pathogenesis. We describe a model of thyroid-stimulating hormone (TSH) receptor (TSHR)/IGF1R crosstalk and present evidence that observations indicating IGF1R's role in GO could be explained by this mechanism. We evaluate the evidence for and against IGF1R as a direct target of stimulating IGF1R antibodies (IGF1RAbs) and conclude that GO pathogenesis does not involve directly stimulating IGF1RAbs. We further conclude that the preponderance of evidence supports TSHR as the direct and only target of stimulating autoantibodies in GO and maintain that the TSHR should remain a major target for further development of a medical therapy for GO in concert with drugs that target TSHR/IGF1R crosstalk.