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A potential role of human RNASET2 overexpression in the pathogenesis of Graves’ disease

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Abstract

Genetic variation of the gene encoding for the only human enzyme of the T2 ribonucleases family (RNASET2) emerged in genome-wide association studies as a putative risk hotspot for Graves’ disease (GD). T2 ribonucleases activities include immune regulation, induction of cell apoptosis and differentiation. Several reports supported the hypothesis that RNASET2 represents a “danger” message addressed to the innate immune system in peculiar conditions. This was a longitudinal, case-control study. RNASET2 protein levels were assessed in blood samples from 34 consecutive newly diagnosed GD patients and in healthy controls. At enrollment, RNASET2 levels were significantly higher in GD patients (98.5 ± 29.1 ng/ml) compared to healthy controls (72.5 ± 27.9 ng/ml, p = 0.001). After 6 months of methimazole treatment, RNASET2 levels significantly decrease and return to levels similar to healthy controls (62.4 ± 22 ng/ml, p = 0.69). These preliminary results suggest that RNASET2 is overexpressed in patients with GD and might represent an “alarm signal” generated by thyroid cells in response to endogenous or environmental stress to alert the immune system.

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Funding

LM was supported by Fondo di Ateneo per la Ricerca FAR 2020, University of Insubria. EP was supported by Fondo di Ateneo per la Ricerca FAR 2018, University of Insubria. LM and FA have received funds from the Italian Ministry of University and Research PRIN 2017 grant (ID: 2017NTK4HY). AB has received funds from the Italian Association for Cancer Research (AIRC-MFAG id 22818) and the Cariplo Foundation (id 2019–1609).

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Author notes

  1. These authors contributed equally: Daniela Gallo, Annarosaria De Vito

  2. These authors jointly supervised this work: Lorenzo Mortara, Francesco Acquati

Authors and Affiliations

  1. Endocrine Unit, Department of Medicine and Surgery, University of Insubria, ASST dei Sette Laghi, 21100, Varese, Italy

    Daniela Gallo, Eliana Piantanida, Luigi Bartalena & Maria Laura Tanda

  2. Human Genetics Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100, Varese, Italy

    Annarosaria De Vito, Rossella Roncoroni & Francesco Acquati

  3. Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100, Varese, Italy

    Antonino Bruno & Lorenzo Mortara

  4. IRCCS MultiMedica, Milan, 20138, Italy

    Antonino Bruno

Authors
  1. Daniela Gallo
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  2. Annarosaria De Vito
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  3. Rossella Roncoroni
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  4. Antonino Bruno
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  5. Eliana Piantanida
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  6. Luigi Bartalena
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  7. Maria Laura Tanda
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  8. Lorenzo Mortara
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  9. Francesco Acquati
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Contributions

All the authors contributed to the manuscript and revised the final version.

Corresponding author

Correspondence to Daniela Gallo.

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Conflict of interest

The authors declare no competing interests.

Ethics approval

This study was performed in line with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. This was a longitudinal observational study. According to the available guideline, patients were treated as per clinical practice with standard anti-thyroid drug treatment and the results on RNASET2 levels did not influence decisions on treatment. The research was included in studies on innate immunity in GD patients approved by the local ethical Committee (ASST dei Sette Laghi, Varese). All data were anonymized.

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Written informed consent was obtained from all individual participants included in the study.

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Gallo, D., De Vito, A., Roncoroni, R. et al. A potential role of human RNASET2 overexpression in the pathogenesis of Graves’ disease. Endocrine 79, 55–59 (2023). https://doi.org/10.1007/s12020-022-03207-4

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  • DOI: https://doi.org/10.1007/s12020-022-03207-4

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