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Serum antibodies against the insulin-like growth factor-1 receptor (IGF-1R) in Graves’ disease and Graves’ orbitopathy

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Abstract

Background

A role of the insulin-like growth factor-1 receptor (IGF-1R) in the pathogenesis of Graves’ orbitopathy (GO) has been proposed, but the existence and function of anti-IGF-1R-antibodies (IGF-1R-Abs) are debated.

Methods

We designed a cross-sectional investigation to measure serum IGF-1R-Abs by a commercial assay in consecutive patients with Graves’ disease (GD) compared with healthy subjects and patients with autoimmune thyroiditis (AT). A total of 134 subjects were screened including 27 healthy subjects, 80 GD patients (54 of whom with GO), and 27 AT patients. The main outcome measure was the prevalence of positive serum IGF-1R-Abs in GO, compared with GD without GO and with the other study groups.

Results

Having established a cut-off value at 55.2 ng/ml for positive tests, positive IGF-1R-Abs were more frequent in GD (25%), than in AT (3.7%, P = 0.003) and healthy subjects (0%, P = 0.006). Within GD, there was no difference between patients with or without GO. Serum levels of IGF-1R-Abs differed across the study population (P < 0.0001), reflecting their higher concentrations in GD (P < 0.0001 vs both AT and healthy subjects), but with no difference between patients with or without GO. In patients with GO, there was an inverse correlation between serum IGF-1R-Abs and CAS (R = − 0.376, 95% CI: from − 0.373 to − 0.631; P = 0.005), the significance of which remains to be investigated.

Conclusions

Serum autoantibodies against the IFG-1R are present in one-fourth of GD patients, regardless of the presence of GO. Further functional studies are needed to investigate the significance of their inverse correlation with GO activity.

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Acknowledgements

The study was funded by the University of Pisa (Fondi di Ateneo, to MM).

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Author notes

  1. E. Sabini

    Present address: Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, MD, USA

Authors and Affiliations

  1. Endocrinology Unit I, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy

    M. Marinò, G. Rotondo Dottore, I. Ionni, G. Lanzolla, E. Sabini, D. Ricci, B. Mazzi, F. Menconi, F. Latrofa, P. Vitti & C. Marcocci

  2. Ophthalmology Unit I, Department of Surgical, Medical and Molecular Pathology, University Hospital of Pisa, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy

    A. Sframeli

  3. Unit of Endocrinology, Department of Internal Medicine and Medical Therapy, University of Pavia, Fondazione Salvatore Maugeri IRCCS, Pavia, Italy

    L. Chiovato

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Correspondence to M. Marinò.

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The authors declare that they have no conflict of interest.

Ethical approval

All diagnostic and therapeutic procedures performed in this study were in accordance with ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the local Ethic Committee (Comitato Etico Regionale per la Sperimentazione Clinica della Regione Toscana; approval number: 13354_MARINO’).

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Marinò, M., Rotondo Dottore, G., Ionni, I. et al. Serum antibodies against the insulin-like growth factor-1 receptor (IGF-1R) in Graves’ disease and Graves’ orbitopathy. J Endocrinol Invest 42, 471–480 (2019). https://doi.org/10.1007/s40618-018-0943-8

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  • DOI: https://doi.org/10.1007/s40618-018-0943-8

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