Thyroid-associated ophthalmopathy (TAO) is a symptom of Graves’ disease. The characteristics of TAO contains orbital inflammation and connective tissue remodeling. Additionally, TAO is a progressive autoimmune disease that leads to the enlargement of orbital fat and extraocular muscles. What’s more. It may potentially disrupt orbital architecture and causes vision loss.
In TAO, the orbit is infiltrated by fibrocytes, bone marrow-derived progenitor cells of the monocyte lineage. Additionally, These cells express fibroblast surface antigens and show high levels of functional TSHR. Fibrocytes from patients with GD express several pro-inflammatory cytokines, including IL-1β, IL-1 receptor antagonist, IL-6, IL-8, and TNFα.
The molecular mechanisms underlying TAO remain obscure. But there exists literature that shows that TSHR and IGF-1R can form a physical and functional complex in orbital fibroblasts and thyroid epithelial cells. Besides, IGF-1R inhibition appears to attenuate TSH-dependent signaling. Researchers suggest that an IGF-1R mAb antagonist may downregulate TSHR- and IGF-1-dependent signaling. And therefore, IGF-1R Inhibition can interrupt pathological activities initiated through both receptors. In this article, we will introduce an IGF-1 receptor (IGF-1R) human monoclonal antibody, Teprotumumab.
Teprotumumab is an IGF-1 receptor (IGF-1R) human monoclonal antibody, that can be used for TAO research.
From: Jain AP, Douglas RS, et al. Clin Exp Ophthalmol. 2021 Mar;49(2):203-211.
It binds to the ligand-binding extracellular α-subunit domain of IGF-1R. Teprotumumab (0-500 μg/mL, 12 h) attenuates the actions of both IGF-1 and TSH in fibrocytes. Additionally, it does not affect IGF-1R and TSHR mRNA abundance after 24 hours. Teprotumumab attenuates TSH-dependent IL-6 and IL-8 expression and Akt phosphorylation. Teprotumumab received its first approval on 21 January 2020 in the US for use in thyroid eye disease.
In summary, Teprotumumab is a potent IGF-1 receptor, that can be used for thyroid-associated ophthalmopathy research.