Affiliation:
1. Medical Research Centre of Endocrinology
Abstract
Current therapeutic approaches to the treatment of endocrine ophthalmopathy (EOP) are based on nonspecific immunosuppression with glucocorticosteroids (GCs) and radiation therapy of the eye orbits. However, some patients exhibit resistance to the treatment. In a previous study, we have detected high levels of soluble cytokine receptors: sTNFα-R1, sTNFα-R2, sIL-2R, and the TGF-β1 cytokine in euthyroid patients with long-lasting non-treated EOP and Graves’ disease (GD). TGF-β1 level was significantly higher in the patients with EOP compared to healthy individuals, and increased with prolonged EOP duration, thus suggesting activation of the factors regulating immune system which promote suppression of the autoimmune process. The aim of this work was to study the dynamics of TGF-β1 and cytokine receptors: sTNFα-R1, sTNFα-R2, sIL-2R in the course of immunosuppressive therapy with high doses of GCs, as possible predictors of treatment efficacy. The study included 49 patients (98 eye orbits) with GD of euthyroid state and subclinical thyrotoxicosis, and the persons with EOP in active phase, who had not previously treatment for EOP. Concentrations of TGF-β1 cytokine, sTNFα-RI and sTNFα-R2, sIL-2R, antibodies to the thyroid-stimulating hormone receptor (rTSH), free fractions of thyroxine (fT4) and triiodothyronine (fT3), TSH in blood serum were determined in blood serum. Ultrasound examination of the thyroid gland (ultrasound of the thyroid gland), multi-layer computed tomography (MSCT)/magnetic resonance imaging (MRI) of the orbits were also performed. The patients were administered immunosuppressive therapy with high doses of HCs (methylprednisolone) in the course of pulse therapy, at a standard dosage of 4500-8000 mg, taking into account the severity and activity of the EOP clinical manifestations. The examination was carried out 3, 6, 12 months after starting the treatment. 3 and 6 months after the GC administration, more than 30% of patients remained resistant to treatment. The levels of TGF-β1 did not change significantly in the patients with positive EOP dynamics. In the patients resistant to GC treatment, the level of TGF-β1 was significantly decreased compared with patients who showed positive clinical dynamics. The level of sNFR1 and sNFaR2 did not change significantly. There were no significant differences in the levels of antibodies to rTSH, thyroid hormones in the patients resistant to GC treatment and with positive dynamics.Immunosuppressive therapy with high-dose of methylprednisolone in pulse therapy regimen showed high efficacy and good tolerability, while some patients remain resistant to treatment. Lower levels of TGF-β1 cytokine at initial time and during the treatment allow usage of TGF-β1 levels as a biomarker of the activity of the process, treatment efficiency, and prognosis of the disease. Activation of TGF-β1, a fibroblast growth factor, may contribute to the development of fibrosis, strabismus, and diplopia.
Subject
Immunology,Immunology and Allergy
Reference27 articles.
1. Sviridenko N.Yu., Bessmertnaya E.G., Belovalova I.M., Mikheenkov A.A., Sheremeta M.S., Nikankina L.V., Malysheva N.M. Autoantibodies, immunoglobulins and cytokine profile in patients with graves’ disease and graves’ orbitopathy. Problemy endokrinologii = Problems of Endocrinology, 2020, Vol. 66, no. 5, pp. 15-23. (In Russ.)
2. Simbirtsev A.S. Cytokines in the pathogenesis of infectious and noninfectious human diseases. Meditsinskiy akademicheskiy zhurnal = Medical Academic Journal, 2013, Vol. 1, no. 3, pp. 18-41. (In Russ.)
3. Simbirtsev A.S. Cytokines in the pathogenesis and treatment of human diseases. St. Petersburg: Foliant, 2018. 512 p.
4. Stagnieva I.V., Boiko N.V., Gukasyan E.L., Bachurina A.S. The role of cytokines in the diagnostics of inflammatory diseases of the upper respiratory tract. Rossiyskaya rinologiya = Russian Rhinology, 2017, Vol. 25, no. 4, pp. 43-47. (In Russ.)
5. Taskina E.S., Kharintseva S.V. Morphofunctional characteristics and immunological regulation of the orbital fibroblasts function in endocrine ophthalmopathy. Klinicheskaya i eksperimentalnaya tireoidologiya = Clinical and Experimental Thyroidology, 2018, Vol. 14, no. 4, pp. 183-191. (In Russ.)
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献