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1.
Probl Endokrinol (Mosk) ; 69(3): 35-43, 2023 Jun 30.
Artigo em Russo | MEDLINE | ID: mdl-37448245

RESUMO

BACKGROUND: The content of regulatory T cells (Treg) at different stages in formation of effector subpopulations and the level of CD25 expression on the membrane of their various fractions in Graves' disease can determine the long-term autoimmune process persistence and be the target of immunotropic therapy of the disease. AIM: To study the features of regulatory T-blood cells subpopulation and the level of CD25 expression in patients with Graves' disease in dynamics after radioactive iodine therapy (RIT) to identify the specific Treg subpopulations for potential immunotropic therapy targets of the disease. MATERIALS AND METHODS: A single-center, prospective, cohort, open, controlled study was conducted with the participation of women with laboratory-confirmed Graves' disease. The features of regulatory T-blood cells subpopulation and the level of expression (MFI) CD25 surface receptor were studied by flow cytometry using direct immunofluorescence using monoclonal antibodies. RESULTS: The study included 36 women with recurrent Graves' disease, middle age 46.34±14.32 years. In patients with Graves' disease before and during the entire period after RIT a low percentage of naive (CD45R0-CD62L+) and terminally differentiated (CD45R0-CD62L-) Treg was established relative to the control, and on 3 and 6 months after RIT a significant decrease of cells with this phenotype was revealed relative to the values detected in patients before and 1 month after RIT (p<0.001). Against the background of compensated hypothyroidism the most significant changes of expression CD25 receptor in patients with Graves' disease were found on 3 and 6 months after RIT: reduced levels of MFI CD25 on surface of naive and terminally differentiated Treg. CONCLUSION: A decrease in the level of naive Treg was found (apparently due to a violation of differentiation processes in thymus) and terminally differentiated Tregs (due to maturation and survival processes), which are supplemented by a reduced expression of the CD25 receptor on the surface of these cells and do not depend on hyperthyroidism compensation, the titer of TSH receptor antibodies, previous conservative therapy with thiamazole and RIT. The obtained new data reveal the role of naive and terminally differentiated Treg subpopulations in immunopathogenesis and help to outline further ways to develop approaches for immunotropic therapy.


Assuntos
Doença de Graves , Neoplasias da Glândula Tireoide , Feminino , Humanos , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Radioisótopos do Iodo/uso terapêutico , Estudos Prospectivos , Neoplasias da Glândula Tireoide/metabolismo
2.
Probl Endokrinol (Mosk) ; 67(6): 39-49, 2021 Nov 09.
Artigo em Russo | MEDLINE | ID: mdl-35018760

RESUMO

BACKGROUND: Effective control of autoimmune inflammation in Graves' disease determines necessity to study the T helper (Th) and cytotoxic T-lymphocytes dysfunction, as well as the level of regulatory T-cells (Treg) activation in patients with Graves' disease on thyrostatic medication, which will clarify the immunomodulatory effects of long-term thiamazole treatment serve as targets for more specific therapies. AIM: To study the phenotypic composition of T-lymphocytes in the peripheral blood of patients with Graves' disease to assess the direction of immune response depending on thimazole-induced euthyroidism duration. MATERIALS AND METHODS: A single-center, cohort, continuous, open-label, controlled trial was conducted to assess the phenotypic composition of T-lymphocytes in peripheral blood in women with Graves' disease on long-term thiamazole treatment. The phenotypic composition of T-lymphocytes was determined by flow cytometry using direct immunofluorescence with conjugated FITC monoclonal antibodies depending on the duration of thimazole-induced euthyroidism of long-term thiamazole treatment. RESULTS: The study included 135 women with Graves' disease, mean age 43.09±12.81 years, 120 (88.91%) with a relapse of the disease and 15 (11.09%) with newly diagnosed hyperthyroidism. An increase of activated CD3+CD4+CD25+ was found in patients with Graves' disease with a duration of thimazole-induced euthyroidism 5-8 months and 9-12 months, respectively, Me=0.94 (0.48-1.45), p=0.020) and Me=0.95 (0.41-1.80), p=0.025), in control group - Me=0.12 (0.03-0.68). Compared to the control an increase of CD4+CD25+CD127Low (Treg) was found in patients with a duration of thimazole-induced euthyroidism 5-8 and 9-12 months. The content of Treg in peripheral blood in Graves' disease patients with a duration of thimazole-induced euthyroidism more than 12 months decreases, but remains elevated relative to the control. CONCLUSION: In patients with Graves' disease with a duration of thimazole-induced euthyroidism 5-8 months and 9-12 months the level of Treg has been increased. The increase of activated Th (CD3+CD4+CD25+) persists independently of thimazole-induced euthyroidism. In patients with Graves' disease with a duration of thimazole-induced euthyroidism for more than 12 months, there is a compensatory increase in regulatory T-lymphocyte, and the total number of T-helpers is restored to the control.


Assuntos
Doença de Graves , Hipertireoidismo , Tratamento Conservador , Feminino , Doença de Graves/tratamento farmacológico , Humanos , Metimazol/efeitos adversos , Linfócitos T Reguladores
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