Therapeutic IGF-I receptor inhibition alters fibrocyte immune phenotype in thyroid-associated ophthalmopathy
Roshini Fernando, Oshadi Caldera, Terry J. Smith
Abstract
Significance Teprotumumab, a therapeutic IGF-I receptor inhibitor, dramatically alters the clinical course of thyroid-associated ophthalmopathy (TAO) and has recently become the only medical therapy for TAO thus far approved by the US FDA. Introduction of teprotumumab has resulted in a paradigm shift in the clinical management of TAO. Here, we demonstrate that teprotumumab and other IGF-I inhibitors attenuate MHC II and B7 expression in fibrocytes in TAO, both in vitro and in patients treated with the drug in vivo. This inhibition is associated with substantial reductions in two key inflammatory cytokines implicated in TAO. Thus, the current findings provide a plausible mechanism underlying the therapeutic responses to teprotumumab.