AUTHOR=Cui Xuejiao , Wang Futao , Liu Cong 

TITLE=A review of TSHR- and IGF-1R-related pathogenesis and treatment of Graves’ orbitopathy

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1062045

DOI=10.3389/fimmu.2023.1062045

ISSN=1664-3224

ABSTRACT=Graves’ orbitopathy (GO) is an organ-specific autoimmune disease. The pathogenesis of GO is 
unclear. There are few review articles on GO research from the perspective of target cells and target 
antigens. A systematic search of PubMed was performed focusing mainly on studies published after 
 2015 that were associated with the role of target cells, orbital fibroblasts (OFs) and orbital adipocytes 
(OAs), target antigens, thyrotropin receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-
 1R), and their corresponding antibodies, TSHR antibodies (TRAbs) and IGF-1R antibodies (IGF-1R 
Abs) in the pathogenesis of GO and the potentially effective therapies for GO that target TSHR and 
 IGF-1R. This review suggests that OFs may be from bone marrow-derived CD34+ fibrocytes. In 
addition to CD34+ OFs, CD34- OFs are important in the pathogenesis of GO and may be involved in 
 hyaluronan formation. CD34- OFs expressing Slit2 suppress the phenotype of CD34+ OFs. β-arrestin 
1 can be involved in TSHR/IGF-1R crosstalk as a scaffold. The study of TRAbs has gradually shifted 
to TSAbs, TBAbs and the titre of TRAbs, but the existence and role of IGF-1R Abs are still unknown 
 and deserve further study. Basic and clinical trials of TSHR-inhibiting therapies are increasing, and 
TSHR is an expected therapeutic target. Teprotumumab has become the latest second-line treatment 
for GO. This review aims to effectively describe the pathogenesis of GO from the perspective of target cells and target antigens and provide ideas for the fundamental treatment of GO.