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Effect of systemic steroid therapy in Graves' orbitopathy on regulatory T cells and Th17/Treg ratio
M Siomkajło1, Ł Mizera2, D Szymczak3
1Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, L. Pasteur 4, 50-367, Wroclaw, Poland. martasiomkajlo@10g.pl.
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.
Insights
Systemic steroid therapy for Graves' orbitopathy did not improve outcomes by altering regulatory T lymphocytes (Tregs) or T helper 17 lymphocytes (Th17). The observed decrease in Tregs was a non-specific steroid effect, not linked to clinical improvement.
Area of Science:
- Immunology
- Endocrinology
- Ophthalmology
Background:
- Graves' orbitopathy is an autoimmune condition affecting the eyes.
- Glucocorticoids are a common treatment, but their mechanism is not fully understood.
- Regulatory T lymphocytes (Tregs) and T helper 17 lymphocytes (Th17) play roles in immune regulation.
Purpose of the Study:
- To investigate if systemic steroid therapy for Graves' orbitopathy impacts Treg and Th17 cell levels.
- To determine if changes in Treg and Th17 cells correlate with treatment effectiveness.
Main Methods:
- 32 patients with active Graves' orbitopathy received methylprednisolone pulses.
- Peripheral blood Treg and Th17 levels were measured via flow cytometry.
- Disease activity, severity, and treatment response were assessed using clinical scores and criteria.
Main Results:
- Methylprednisolone improved disease activity but altered the Th17/Treg balance.
- The percentage of Tregs decreased, while Th17 cell numbers remained stable.
- No correlation was found between the Treg/Th17 ratio and disease activity, severity, or treatment outcomes.
Conclusions:
- Steroid therapy's benefits in Graves' orbitopathy are not mediated by peripheral Treg/Th17 changes.
- The reduction in Treg percentage is likely a non-specific steroid effect.
- Peripheral Treg and Th17 levels do not predict clinical outcomes in this context.
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