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Purpose <p>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.</p> Methods <p>We conducted a cross-sectional study to investigate IGF-1R-Abs in 147 consecutive Graves’ disease (GD) patients, with (<i>n</i> = 92) or without (<i>n</i> = 55) GO (primary outcome), their relationship with GO features and their effect on cell proliferation in primary cultures of orbital fibroblasts.</p> Results <p>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, <i>P</i> = 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 <i>vs</i> 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, <i>P</i> = 0.035). Incubation of orbital fibroblasts from GO patients with IgGs purified from a pool of sera with IGF-1R-Abs &gt; 55 ng/mL decreased cell proliferation in a dose-dependent manner (Omega square = 0.747; <i>P</i> &lt; 0.0001).</p> Conclusions <p>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.</p>

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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

  • 期刊论文

  • 发表日期：

    2025年3月29日

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  • Giulia Lanzolla,
  • Giovanna Rotondo Dottore,
  • Simone Comi,
  • Giada Cosentino,
  • Dalì Antonia Ciampa,
  • Elena Sabini,
  • Francesca Menconi,
  • Maria Novella Maglionico,
  • Chiara Posarelli,
  • Roberto Rocchi,
  • Francesco Latrofa,
  • Michele Figus,
  • Ferruccio Santini,
  • Michele Marinò

摘要

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.