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

Christine C Krieger,Susanne Neumann,Marvin C Gershengorn

doi:10.3390/ijms21186561

Abstract

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.

Highlights

Graves’ orbitopathy (GO) has been under intense study with a goal to understand its pathogenesis and to aid in the development of medical therapies
It remains controversial as to whether there are autoantibodies that bind to and directly activate insulin-like growth factor 1 (IGF1) receptors (IGF1Rs) [8,9]. It appears that cell-mediated immunity plays a role in GO, and it is possible that there are TSH receptors (TSHRs) and IGF1Rs on lymphocytes that may be involved; these receptors would have to be activated by the antibodies
An alternative possibility for the involvement of IGF1Rs in GO pathogenesis is that IGF1R involvement results not from stimulating IGF1RAbs but from crosstalk of IGF1Rs with TSHRs that are activated by TSAbs [11]

Summary

Introduction

Graves’ orbitopathy (GO) ( termed Graves’ ophthalmopathy, thyroid-associated ophthalmopathy or thyroid eye disease) has been under intense study with a goal to understand its pathogenesis and to aid in the development of medical therapies. It remains controversial as to whether there are autoantibodies that bind to and directly activate IGF1Rs (stimulating IGF1RAbs) [8,9].

Results

Conclusion