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Effect of systemic steroid therapy in Graves’ orbitopathy on regulatory T cells and Th17/Treg ratio

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Abstract

Purpose

Glucocorticoids are a mainstay treatment for Graves’ orbitopathy, yet their exact mechanisms of action remain unclear. We aimed to determine whether the therapeutic effects of systemic steroid therapy in Graves’ orbitopathy are mediated by changes in regulatory T lymphocytes (Tregs) and T helper 17 lymphocytes (Th17).

Methods

We assessed Treg and Th17 levels in the peripheral blood of 32 patients with active, moderate-to-severe Graves’ orbitopathy who received 12 weekly pulses of methylprednisolone, and determined their association with disease severity, disease activity, and treatment outcomes. The acute orbitopathy phase was confirmed based on clinical evaluation and magnetic resonance imaging, and assessed using the clinical activity score (CAS). The severity of the disease was classified according to ETA/EUGOGO guidelines, and quantified based on the total eye score. Treatment response was determined based on specific criteria (e.g., changes in CAS score, diplopia grade, visual acuity, etc.). Treg and Th17 cells were identified using flow cytometry.

Results

Methylprednisolone treatment improved the activity of the disease and altered the Th17/Treg balance (i.e., the percentage of Tregs decreased while the number of Th17 cells remained unchanged). There was no association between the Treg/Th17 ratio and the activity and severity of the disease or the treatment response.

Conclusions

Therapeutic effects of steroid therapy in Graves’ orbitopathy are not mediated by Treg and Th17 alterations in the peripheral blood. The decrease in peripheral Treg percentage is likely a consequence of the non-specific effects of steroids and does not impact clinical outcome.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank Proper Medical Writing sp. z o. o for the professional language and technical corrections for this manuscript

Funding

This work was supported by funds from the Wroclaw Medical University (STM.C120.16.016).

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Authors and Affiliations

  1. Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, L. Pasteur 4, 50-367, Wroclaw, Poland

    M. Siomkajło, Ł. Mizera, K. Kolačkov, M. Bolanowski & J. Daroszewski

  2. Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, L. Pasteur 4, 50-367, Wroclaw, Poland

    D. Szymczak

  3. Department of Human Morphology and Embryology, Wroclaw Medical University, T. Chalubinskiego 6a, 50-368, Wroclaw, Poland

    J. Grzegrzółka

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  1. M. Siomkajło
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Correspondence to M. Siomkajło.

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Siomkajło, M., Mizera, Ł., Szymczak, D. et al. Effect of systemic steroid therapy in Graves’ orbitopathy on regulatory T cells and Th17/Treg ratio. J Endocrinol Invest 44, 2475–2484 (2021). https://doi.org/10.1007/s40618-021-01565-w

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