In vivo and in vitro evidence for a protective role of autoantibodies against the insulin-like growth factor-1 receptor (IGF-1R) in Graves' orbitopathy

Purpose: The insulin-like growth factor-1 receptor (IGF-1R) plays a role in the pathogenesis of Graves’ orbitopathy (GO). A possible protective role of autoantibodies against IGF-1R (IGF-1R-Abs) on GO has been suggested. Methods: We conducted a cross-sectional study to investigate IGF-1R-Abs in 147 consecutive Graves’ disease (GD) patients, with (n = 92) or without (n = 55) GO (primary outcome), their relationship with GO features and their effect on cell proliferation in primary cultures of orbital fibroblasts. Results: Serum IGF-1R-Abs levels were higher (29.3 ng/mL, IQR 17.4–36.6) in patients without GO than in those with GO (19.8 ng/mL, IQR 11.2–29.8; Mann Whitney U 1819, P = 0.00509). The prevalence of IGF-1R-Abs levels above the previously established cut-off value of 55 ng/mL did not differ statistically between the two groups, despite a trend towards a greater prevalence in patients without GO (9 vs 3.2%) (Fig. 1b). Within GO patients, serum IGF-1R-Abs did not correlate with proptosis, CAS, eyelid width and visual acuity, whereas there was an inverse correlation with diplopia, being IGF-1R-Abs lower in patients with the most severe degrees (Omega square = 0.0123, P = 0.035). Incubation of orbital fibroblasts from GO patients with IgGs purified from a pool of sera with IGF-1R-Abs > 55 ng/mL decreased cell proliferation in a dose-dependent manner (Omega square = 0.747; P < 0.0001). Conclusions: Serum autoantibodies against the IGF-1R are present in a minority of patients with GD and seem to exert a protective role on GO development and features.