Abstract
Purpose :
IGF-1 receptor (IGF-1R) pathway was shown to be involved at critical processes pertaining to the pathogenesis of Thyroid-Associated Orbitopathy (TAO) and the recent breakthrough in a double-masked, randomized controlled trial using humanized monoclonal antibody inhibitor of IGF-IR (teprotumumab) in patients with active TAO further reinforced its roles. We hypothesize that IGF-1R positive PBMC exit circulation and infiltrate to the orbital tissues. We prospectively compared the level of expression of IGF-1R in peripheral blood mononuclear cells (PBMC) in patients with progressive Thyroid-Associated Orbitopathy (TAO) before any immunosuppressive treatment and those with only Graves Disease (GD) but no clinically evident TAO.
Methods :
Euthyroid patients who were referred for recent-onset (<9-month), progressive TAO (n=20) as well as those with GD only (n=20) were recruited. The presence of orbitopathy and disease activity were evaluated by a single oculoplastic surgeon. PBMC were prepared from venous blood, isolated by red cell lysis, fixed and stained by masked laboratory personnel while isotype control was prepared by staining with secondary antibody only. IGF-1R expressions were measured using flow cytometry (FACS Calibur, BD Biosciences). Percentage of IGF-1R positive expression was determined as the population of gated viable cells with increased fluorescent intensity compared with those in isotype control.
Results :
Age, gender, smoking and family history, use of antithyroid medication, thyroxine supplement or radioactive iodide, duration of GD as well as the most recent thyroid function were not significantly different between groups (all p>0.5). Patients with GD alone show significantly more circulating IGF1R positive PBMC than patients with TAO (99+/-4% vs 65+/-5%, p < 0.01, Mann-Whitney test).
Conclusions :
Percentage of IGF-1R positive PBMC was found to be lower in patients with recent-onset TAO compared to those with GD only. Serially monitoring of IGF-1R expression in PBMC may be a surrogate biomarker to identify GD patients at risk of developing progressive TAO.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.