RESUMO
In recent years, Hashimoto's thyroiditis (HT) has become the most common autoimmune thyroid disease. It is characterized by lymphocyte infiltration and the detection of specific serum autoantibodies. Although the potential mechanism is still not clear, the risk of Hashimoto's thyroiditis is related to genetic and environmental factors. At present, there are several types of models of autoimmune thyroiditis, including experimental autoimmune thyroiditis (EAT) and spontaneous autoimmune thyroiditis (SAT). EAT in mice is a common model for HT, which is immunized with lipopolysaccharide (LPS) combined with thyroglobulin (Tg) or supplemented with complete Freund's adjuvant (CFA). The EAT mouse model is widely established in many types of mice. However, the disease progression is more likely associated with the Tg antibody response, which may vary in different experiments. SAT is also widely used in the study of HT in the NOD.H-2h4 mouse. The NOD.H2h4 mouse is a new strain obtained from the cross of the nonobese diabetic (NOD) mouse with the B10.A(4R), which is significantly induced for HT with or without feeding iodine. During the induction, the NOD.H-2h4 mouse has a high level of TgAb accompanied by lymphocyte infiltration in the thyroid follicular tissue. However, for this type of mouse model, there are few studies to comprehensively evaluate the pathological process during the induction of iodine. A SAT mouse model for HT research is established in this study, and the pathologic changing process is evaluated after a long period of iodine induction. Through this model, researchers can better understand the pathological development of HT and screen new treatment methods for HT.
Assuntos
Iodo , Tireoidite Autoimune , Camundongos , Animais , Tireoidite Autoimune/genética , Tireoidite Autoimune/patologia , Autoanticorpos , Camundongos Endogâmicos NOD , Suplementos Nutricionais , Modelos Animais de DoençasRESUMO
PURPOSE: Autoimmune thyroiditis (AIT) is one of the most common autoimmune endocrine diseases. The currently recognized causes are genetic susceptibility, environmental factors and immune disorders. It is important to clarify the pathogenesis for the prevention, diagnosis, treatment of AIT and scientific iodine supplementation. This study analyzed the DNA methylation levels of PRKAA2, ITGA6, PRL and THEM4 genes related to PI3K-AKT signaling pathway, compared the DNA methylation levels between cases and controls from different water iodine levels in Shandong Province of China, and evaluated the contribution of PI3K-AKT signaling pathway-related genes in AIT. METHODS: A total of 176 adult AIT patients were included from three different water iodine areas, and 176 healthy controls were included according to gender, age and BMI. According to the results of the Illumina Methylation 850 K BeadChip in our previous research, the significant methylation differences of genes on the PI3K-AKT signaling pathway related to AIT were determined. The MethylTarget™ assay was used to detect the methylation levels of the target genes, and real-time PCR experiments were used to verify the mRNA expression levels. RESULTS: Compared with the control group, PRKAA2_3 and 15 CpG sites were hyper-methylated. ITGA6 gene and 2 CpG sites were hypo-methylated in AIT cases. The mRNA expression of ITGA6 gene was negatively correlated with the DNA methylation levels of ITGA6 gene and 2 CpG sites. Compared with cases and controls in areas with different water iodine levels, methylation differences were mainly in PRKAA2 and ITGA6 genes. The methylation levels of PRKAA2_1 and PRKAA2_3 were positively correlated with age. The methylation levels of PRL and THEM4 genes were negatively correlated with age. The methylation level of PRKAA2_3 was positively correlated with FT4. CONCLUSION: In summary, we identified aberrant DNA methylation levels of PRKAA2 and ITGA6 genes related to PI3K-AKT signaling pathway in the blood of AIT patients. Both iodine supplementation after long-term iodine deficiency and iodine excess can affect the DNA methylation levels of PRKAA2 and ITGA6 genes, and the former affects more obviously. In ITGA6 gene, this aberrant epigenetic modification is associated with the increased mRNA expression.
Assuntos
Doença de Hashimoto , Iodo , Tireoidite Autoimune , Adulto , Metilação de DNA , Humanos , Integrina alfa6/genética , Integrina alfa6/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Tireoidite Autoimune/genética , Tireoidite Autoimune/patologia , ÁguaRESUMO
BACKGROUND: High mobility group box-1 (HMGB1), a non-histone protein, plays an important role in autoimmune diseases. However, the significance of HMGB1 in the pathogenesis of autoimmune thyroiditis has not been reported. The purpose of this study was to explore whether HMGB1 participates in the pathogenesis of autoimmune thyroiditis, and whether glycyrrhizin (GL), a direct inhibitor of HMGB1, attenuates the severity of thyroid inflammatory infiltration in a murine model of autoimmune thyroiditis. METHODS: A total of 80 male NOD.H-2h4 mice were randomly divided into a control or iodine supplement (NaI) group at four weeks of age, and the control group was fed with regular water, whereas the NaI group was supplied with 0.005% sodium iodine water. Another 24 male NOD.H-2h4 mice were also randomized into three groups (eight mice per group) as follows: control, NaI, and GL treatment after iodine supplementation (NaI + GL). The NOD.H-2h4 mice were fed with 0.005% sodium iodide water for eight weeks to enhance autoimmune thyroiditis. After iodine treatment, the mice received intraperitoneal injections of GL for four weeks. The severity of lymphocytic infiltration in the thyroid gland was measured by histopathological studies. The serum levels of HMGB1, tumor necrosis factor alpha, interleukin (IL)-6, IL-1ß, and thyroglobulin antibody titers were measured using an enzyme-linked immunosorbent assay. HMGB1 expression was measured by immunohistochemical staining and real-time polymerase chain reaction. TLR2, HMGB1, MyD88, and nuclear transcription factor κB were measured by Western blot. RESULTS: The mRNA expression of HMGB1 was significantly higher at 8 and 16 weeks in the NaI group than it was in the control group. Serum levels of thyroglobulin antibodies, HMGB1, tumor necrosis factor alpha, IL-6, and IL-1ß were significantly increased in the NaI group, but they were dramatically attenuated with GL injection. The prevalence of thyroiditis and the infiltration of lymphocytes were significantly decreased in the NaI + GL group. GL administration also significantly reduced the protein expression of TLR2, MyD88, HMGB1 and nuclear transcription factor κB in the thyroid gland and attenuated the severity of thyroiditis. CONCLUSION: HMGB1 may play a crucial role in autoimmune thyroiditis by causing inflammatory infiltration, thus increasing the severity of autoimmune thyroiditis. GL effectively attenuated thyroiditis in the iodine-induced NOD.H-2h4 mice via a molecular mechanism related to the inhibition of TLR2-HMGB1 signaling.
Assuntos
Anti-Inflamatórios/farmacologia , Ácido Glicirrízico/farmacologia , Proteína HMGB1/antagonistas & inibidores , Inflamação/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Tireoidite Autoimune/tratamento farmacológico , Receptor 2 Toll-Like/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Citocinas/sangue , Modelos Animais de Doenças , Ácido Glicirrízico/uso terapêutico , Proteína HMGB1/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , Iodeto de Sódio , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Tireoidite Autoimune/induzido quimicamente , Tireoidite Autoimune/metabolismo , Tireoidite Autoimune/patologiaRESUMO
Maternal hormones are essential for the normal fetal development during pregnancy. Autoimmune thyroid disease is a frequent pathology in our iodine replete region. The aim of this study is to evaluate the occurrence of subclinical hypothyroidism (SCH) in cases with known autoimmune thyroid disease, which were in a euthyroid state prior to pregnancy, and to assess the association between supplemental treatments administered and the outcome of the pregnancy. The study is a prospective interventional controlled study. The two cohorts comprise the interventional group, consisting of 109 pregnant women with known autoimmune asymptomatic thyroid disease, without any levothyroxine (LT4) treatment and an aged-matched control group, with an unknown thyroid disease. After the pregnancy, a monthly evaluation of TSH, FT3, and FT4 was performed. Offspring evaluation was made at birth time. 88.8% of the women developed SCH in the first four weeks of pregnancy. Average LT4 doses increased as the pregnancy progressed. The monthly adjustment was 12.5 or 25 µg. All SCH cases developed in the first trimester of pregnancy. There was no significant difference regarding the gestational week, weight, or length at birth between the interventional group and controls, when TSH values were in the optimal range, during the whole pregnancy. Premature birth was described in one case in the interventional group.
Assuntos
Autoanticorpos/sangue , Medicina de Precisão , Glândula Tireoide/efeitos dos fármacos , Tireoidite Autoimune/tratamento farmacológico , Tiroxina/uso terapêutico , Adulto , Doenças Assintomáticas , Estudos de Casos e Controles , Monitoramento de Medicamentos , Feminino , Seguimentos , Idade Gestacional , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Tireoidite Autoimune/sangue , Tireoidite Autoimune/diagnóstico , Tireoidite Autoimune/patologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
Hashimoto's thyroiditis (HT) is one of the most common organ-specific autoimmune diseases. Increasing evidence indicates that HT may be characterized by an imbalance in the helper T cell subsets Th1 and Th2. Traditional Chinese Medicine (TCM) considers HT as a chronic exhaustion disease, leading to deficiency of qi. In TCM, qi indicates the functional power of the organs of the human body; hence TCM recommends focusing the treatment of HT so as to increase qi production. Ginseng is a well-known herbal medicine exhibiting a variety of efficacies, its main function-being to generate qi. Ginseng's principal active component is ginsenoside, and modern pharmacology has shown that ginsenoside demonstrates biphasic immunomodulatory effects that can be utilized for the treatment of immune disorders. Previous work demonstrated that ginsenoside has a therapeutic effect on HT, but its mechanism is unknown. Experimental autoimmune thyroiditis rats were produced in order to investigate whether ginsenoside can modulate Th1/Th2 imbalance, the direct objective being to examine modulation of IFN-γ and IL-4 by ELISA, and the gene and protein expression of T-bet and GATA-3 by real-time PCR and Western blot. IFN-γ levels were increased while IL-4 levels decreased in EAT rats; treatment with ginsenoside led to decreased peripheral blood IFN-γ levels, with low doses statistically significant. Ginsenoside produced a biphasic effect on IL-4, with low and moderate doses promoting and high doses inhibiting secretion. Both protein and mRNA levels of T-bet were markedly reduced, while GATA-3 was significantly increased by ginsenoside.
Assuntos
Fator de Transcrição GATA3/genética , Ginsenosídeos/farmacologia , Proteínas com Domínio T/genética , Tireoidite Autoimune/genética , Animais , Modelos Animais de Doenças , Feminino , Fator de Transcrição GATA3/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/uso terapêutico , Doença de Hashimoto/tratamento farmacológico , Doença de Hashimoto/genética , Medicina Tradicional Chinesa , Ratos , Ratos Wistar , Proteínas com Domínio T/metabolismo , Tireoidite Autoimune/tratamento farmacológico , Tireoidite Autoimune/patologiaRESUMO
In the field of autoimmune thyroiditis, NOD.H2(h4) mice have attracted significant and increasing attention since they not only develop spontaneous disease but they present thyroiditis with accelerated incidence and severity if they ingest iodide through their drinking water. This animal model highlights the interplay between genetic and dietary factors in the triggering of autoimmune disease and offers new opportunities to study immunoregulatory parameters influenced by both genes and environment. Here, we review experimental findings with this mouse model of thyroiditis.
Assuntos
Autoimunidade , Meio Ambiente , Interação Gene-Ambiente , Animais , Autoanticorpos/imunologia , Autoimunidade/genética , Linfócitos B/imunologia , Linfócitos B/metabolismo , Citocinas/genética , Citocinas/metabolismo , Suplementos Nutricionais/efeitos adversos , Modelos Animais de Doenças , Expressão Gênica , Humanos , Iodetos/efeitos adversos , Camundongos , Camundongos Endogâmicos NOD , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Tireoglobulina/imunologia , Tireoidite Autoimune/etiologia , Tireoidite Autoimune/metabolismo , Tireoidite Autoimune/patologiaRESUMO
This article presents the background for including phytopreparation Alba (root extract of the Potentilla alba) into complex treatment of thyroid pathology. The findings confirm visible reduction of size of the thyroid gland and normalizing its functions in children and adults with the thyroid gland with normal or enhanced function treated by Alba per oral.
Assuntos
Bócio Endêmico/tratamento farmacológico , Bócio Nodular/tratamento farmacológico , Hipotireoidismo/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Potentilla/química , Tireoidite Autoimune/tratamento farmacológico , Tireotoxicose/tratamento farmacológico , Administração Oral , Adolescente , Criança , Feminino , Bócio Endêmico/patologia , Bócio Nodular/patologia , Humanos , Hipotireoidismo/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/patologia , Tireoidite Autoimune/patologia , Tireotoxicose/patologiaRESUMO
BACKGROUND: The impact of excessive iodine intake on the development of autoimmune thyroiditis (AIT) is still under debate. Transgenic, antibody-devoid TAZ10 mice spontaneously develop AIT due to autoreactive thyroperoxidase-specific T cells. In this model, development of AIT is determined by a T cell infiltration of the thyroid gland leading to an elevation of serum thyrotropin (TSH) levels and significant weight gain. In the present study we investigated the impact of moderate and high iodine supplementation on the course of disease in these mice, which are immunologically prone to AIT. METHODS: In addition to normal nutrition, mice were supplemented for 20 weeks with 2.5 µg versus 5 µg iodine per milliliter drinking water, which corresponds to a human daily iodine supplementation of 150 µg, 315 µg, and 615 µg iodine. AIT-defining parameters (weight gain, elevation of serum TSH levels, cellular infiltration of the thyroid) and immunologic effects were analyzed. RESULTS: No significant differences were displayed when comparing weight and serum TSH levels in the iodine-supplemented versus control groups. Increased thyroid infiltrates with CD8⺠T cells were detected by fluorescein-activated cell sorter (FACS) and immunofluorescence staining in mice supplemented with elevated iodine amounts (315 µg and 615 µg iodine per day, respectively). Immunologic monitoring revealed selective changes in immune cell frequencies (CD8⺠and regulatory T cells, natural killer [NK] cells) and cytokine production (interferon-γ, interleukin-1α, and interleukin-17), however, without affecting the overall immune balance. CONCLUSION: Our results demonstrate that elevated iodine supplementation has no physical impact on the course of disease in transgenic, antibody-devoid TAZ10 mice, which are immunologically prone to AIT.
Assuntos
Suplementos Nutricionais , Imunidade Celular , Fatores Imunológicos/uso terapêutico , Iodo/uso terapêutico , Células Th1/imunologia , Glândula Tireoide/imunologia , Tireoidite Autoimune/dietoterapia , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Citocinas/sangue , Citocinas/metabolismo , Feminino , Fatores Imunológicos/administração & dosagem , Iodo/administração & dosagem , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , Masculino , Camundongos Transgênicos , Tamanho do Órgão , Organismos Livres de Patógenos Específicos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Células Th1/metabolismo , Células Th1/patologia , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Tireoidite Autoimune/imunologia , Tireoidite Autoimune/metabolismo , Tireoidite Autoimune/patologia , Tireotropina/sangue , Aumento de PesoRESUMO
AIM: The aim of the study was to evaluate the role of selenium (Se) in childhood autoimmune thyroiditis regarding its effect on thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibody (TgAb), and thyroid morphology. METHODS: Newly diagnosed 23 euthyroid children (mean age, 12.3 +/- 2.4 years) with Hashimoto thyroiditis (HT) received only 50 microg L-selenomethionine per day for 3 months. The baseline basal urinary iodine level, serum Se, TSH, fT4, TPOAb, and TgAb concentrations, and thyroid morphology by ultrasound were detected. We reanalyzed the TPOAb and TgAb changes at the 3rd month and then compared the thyroid morphology with 30 healthy individuals (mean age, 12.1 +/- 2.1 years) at the 6th month. RESULTS: Serum TPOAb, TgAb, and thyroid echogenicity were unchanged with Se supplementation. A prominent decrease in thyroid volume was noteworthy; 35% of patients showed a thyroid volume regression rate of > or = 30%. CONCLUSION: In terms of TPOAb and TgAb, Se may not benefit in the euthyroid period of HT, but Se supplementation seems to lead a favorable response in thyroid volume regression.
Assuntos
Selênio/administração & dosagem , Tireoidite Autoimune/tratamento farmacológico , Administração Oral , Adolescente , Idade de Início , Autoanticorpos/sangue , Criança , Feminino , Humanos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Projetos Piloto , Selênio/sangue , Selênio/farmacologia , Testes de Função Tireóidea , Tireoidite Autoimune/sangue , Tireoidite Autoimune/epidemiologia , Tireoidite Autoimune/patologia , Tireotropina/sangueRESUMO
AIM: The aim of this study was to investigate the impact of a novel nanoemulsion (NE) adjuvant, a soybean oil emulsion, on autoimmune response. To this end, we used murine thyroglobulin (mTg)-induced experimental autoimmune thyroiditis in mice as a study model. MATERIALS & METHODS: Mice received NE or NE + mTg by nasal delivery. At 1 week after the second nasal delivery of NE with or without mTg, all mice were immunized with mTg and lipopolysaccharides to induce experimental autoimmune thyroiditis. RESULTS: Compared with controls, mTg-NE-treated mice had much more antigens accumulated in the nasal passage and thymus and developed a milder form of thyroiditis. This was accompanied by an increase in IL-10, IL-17 and reduced IFN-γ. The production of anti-mTg antibodies was significantly decreased in mTg-NE-treated mice. The percentage of Tregs in cervical lymph nodes was higher in mTg-NE-treated mice than NE-treated mice. Furthermore, Foxp3 and TGF-ß levels were prominently enhanced in mTg-NE-treated mice. CONCLUSION: This study indicates that a low dose of mTg in NE can significantly enhance antigen uptake and Tregs, resulting in inhibition of experimental autoimmune thyroiditis development.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Emulsões/uso terapêutico , Tolerância Imunológica , Óleo de Soja/uso terapêutico , Tireoglobulina/administração & dosagem , Tireoglobulina/imunologia , Tireoidite Autoimune/prevenção & controle , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Animais , Autoanticorpos/imunologia , Emulsões/administração & dosagem , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Expressão Gênica , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-17/imunologia , Camundongos , Camundongos Endogâmicos CBA , RNA Mensageiro/genética , Óleo de Soja/administração & dosagem , Óleo de Soja/imunologia , Linfócitos T Reguladores/imunologia , Glândula Tireoide/imunologia , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Tireoidite Autoimune/imunologia , Tireoidite Autoimune/patologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/imunologiaRESUMO
Selenium (Se) is an important element that exerts its effects on the selenoproteins. It is an essential component of the glutathione peroxidase enzymes, which have anti-oxidant and anti-inflammatory properties, and a component of iodothyronine selenodeiodinases, which catalyze the extrathyroid production of T3 from T4. Se is important to several aspects of thyroid homeostasis and may influence the natural course of thyroid diseases such as autoimmune thyroiditis (AIT). This review analyzes the effects of Se supplementation in patients with AIT, based on the studies published on this issue to date.
Assuntos
Suplementos Nutricionais , Progressão da Doença , Selênio/uso terapêutico , Tireoidite Autoimune/tratamento farmacológico , Tireoidite Autoimune/patologia , Animais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the regulatory mechanism of Xiaoyin Recipe () on the T helper 1/T helper 2 (Th1/Th2) immune balance. METHODS: Thirty-six experimental animals were divided into three groups, 12 rats in each group: blank control group (B group), negative control group (N group), and Xiaoyin Recipe treatment group (T group). The latter two groups received immunization of experimental autoimmune thyroiditis (EAT), and T group were treated with Xiaoyin Recipe for a month. Then, the expression of Th1-Th2-related genes in peripheral blood mononuclear cells (PBMCs) were screened with Oligo GEArray Rat Th1-Th2-Th3 Microarray. The expressions of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), T-box expressed in T-cells (T-bet), and GATA-binding protein-3 (GATA-3) were detected by real-time polymerase chain reaction (RT-PCR). RESULTS: Gene array screening showed that compared to N group, in T group after Xiaoyin Recipe treatment, 3 genes were upregulated in EAT rats, including interleukin-27 receptor alpha (IL-27rα), glomulin (Glmn), and GATA-3, while 38 genes were downregulated, such as CD28, IL-18, signal transducer, and activator of transcription 1 (STAT1), T-bet, TNF receptor superfamily member 4 (TNFRSF4), TNF ligand superfamily member 5 (TNFSF5), and TNF receptor superfamily member 5 (TNFRSF5). While RT-PCR showed that there was an increased level of TNF-α mRNA (P<0.01), an elevated ratio of T-bet/GATA-3, and a decreased level of IL-10 mRNA in PBMC of N and T group compared to B group (P <0.01); and after treatment with Xiaoyin Recipe, IL-10 mRNA level increased (P <0.01), while TNF-α mRNA level and T-bet/GATA-3 ratio decreased in T group compared to N group (P <0.01). CONCLUSION: Xiaoyin Recipe for psoriasis could induce a Th1/Th2 balance drift toward Th2 in PBMC of EAT rats and thus improve the conditions.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Psoríase/tratamento farmacológico , Psoríase/imunologia , Equilíbrio Th1-Th2 , Células Th2/imunologia , Tireoidite Autoimune/sangue , Tireoidite Autoimune/tratamento farmacológico , Animais , Autoanticorpos/sangue , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-10/genética , Interleucina-10/metabolismo , Psoríase/sangue , Psoríase/patologia , Ratos , Ratos Wistar , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Equilíbrio Th1-Th2/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Tireoidite Autoimune/imunologia , Tireoidite Autoimune/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Hashimoto's thyroiditis (HT) is a autoimmune disease that is highly incident year by year. Its clinical manifestations are alternative hyperthyroidism or hypothyroidism, relatively high Th1, excessively low Th2 and constantly increasing TGAb and TMAB. Currently, the disease is still difficult to be cured, and instable thyroid function makes it harder to be treated. Therefore, this essay makes a summary analysis on domestic and foreign studies on HT's pathogenesis, clinical manifestations and treatment, resulting that pure supplement or immunosuppressive therapy is hard to achieve notable efficacy, while existing traditional Chinese medicines could only mitigate clinical symposiums but did not reduce inflammation. Therefore, to look for methods and drugs for adjusting immunity imbalance by decreasing Th1 cell factors and increasing Th2 cell factors is significant to HT treatment to some extent.
Assuntos
Tireoidite Autoimune/tratamento farmacológico , Animais , Autoanticorpos/imunologia , Feminino , Humanos , Linfócitos T Auxiliares-Indutores/imunologia , Tireoidite Autoimune/imunologia , Tireoidite Autoimune/patologiaRESUMO
Selenium (Se) is required for thyroid hormone synthesis and metabolism. Se treatment reduces serum thyroidspecific antibody titers in patients with autoimmune thyroiditis (AIT), but the exact mechanism is not clear. We investigated the effects of Se treatment on CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) in a iodine-induced autoimmune thyroiditis model. NOD.H-2(h4) mice were randomly divided into control, AIT untreated, and AIT with Se treatment groups. Mice were fed with 0.005% sodium iodine (NaI) water for 8 weeks to induce AIT. Se-treated mice received 0.3 mg/L sodium selenite in drinking water. The AIT mice had fewer Treg cells and reduced Foxp3 mRNA expression in splenocytes compared with the controls (p < 0.01). The percentage of Treg cells and expression of Foxp3 mRNA were increased by Se treatment (as compared with untreated AIT mice, p < 0.05). Mice that received Se supplementation also had lower serum thyroglobulin antibody (TgAb) titers and reduced lymphocytic infiltration in thyroids than untreated AIT mice. These data suggest that CD4(+)CD25(+) T cells play an important role in the development of AIT. Se supplementation may restore normal levels of CD4(+)CD25(+) T cells by up-regulating the expression of Foxp3 mRNA in mice with AIT.
Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Selênio/farmacologia , Linfócitos T Reguladores/patologia , Tireoidite Autoimune/imunologia , Animais , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Suplementos Nutricionais , Modelos Animais de Doenças , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Iodo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Linfócitos T Reguladores/metabolismo , Tireoidite Autoimune/induzido quimicamente , Tireoidite Autoimune/patologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologiaRESUMO
OBJECTIVE: Our study aimed to investigate whether physiological doses of selenium (Se) influence the natural course of autoimmune thyroiditis (AIT). DESIGN AND PATIENTS: A total of 76 consecutive patients (65 F, 11 M, median 43, range 15-75 years) with AIT, normal or slightly elevated TSH and fT4 within the normal range were divided into two groups: Group 0 (30 cases) was given no treatment while Group 1 (46 cases) was treated with sodium selenite 80 µg/day as a single oral dose for 12 months. Thyroperoxidase and thyroglobulin autoantibodies (TPO-Ab; Tg-Ab), TSH, fT4 and urine iodine concentrations (UIC) were measured at baseline and after 6 and 12 months of follow-up. Thyroid ultrasonography (US) was performed at each follow-up point. Echogenicity was measured by histographic analysis of gray-scale pixels (gsp) ranging from 0 = black to 255 = white. RESULTS: Thyroid echogenicity decreased significantly in both groups after 6 months, but after 12 months, it had changed no more in Group 1, whereas it had dropped further in Group 0. No significant variation in TPO-Ab or Tg-Ab levels was observed between the two groups after 6 months, but both values decreased significantly after 12 months in Group 1, and five patients in this group became negative for TPO-Ab. TSH and FT4 showed no significant variations in either group. CONCLUSIONS: Dietary supplementation with physiological doses of Se seems to be effective in preventing a reduction in thyroid echogenicity after 6 months of treatment and in reducing TPO-Ab and Tg-Ab after 12 months, but does not modify TSH or FT4.
Assuntos
Selenito de Sódio/administração & dosagem , Tireoidite Autoimune/tratamento farmacológico , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Suplementos Nutricionais , Feminino , Humanos , Iodeto Peroxidase/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tireoglobulina/imunologia , Glândula Tireoide/patologia , Tireoidite Autoimune/imunologia , Tireoidite Autoimune/patologia , Tireotropina/sangueRESUMO
Autoimmune thyroiditis (AIT) is an autoimmune disease with genetic background. Women are more likely to develop AIT. In adulthood, AIT is the most frequent cause for acquired hypothyroidism. Cytotoxic T-lymphocyte antigen (CTL-4) may play a role in the etiology of the disease. Diagnosis is made by determination of elevated antibodies against thyroid peroxidase and thyroglobulin, and a hypoechoic pattern in ultrasound. In case of hypothyroidism a substitutive therapy with levothyroxine is necessary. AIT may occur as postpartum thyroiditis or as a special entity as consequence of therapy with cytokines.
Assuntos
Tireoidite Autoimune/diagnóstico , Adulto , Autoanticorpos/sangue , Biópsia por Agulha Fina , Criança , Estudos Transversais , Diagnóstico Diferencial , Feminino , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/epidemiologia , Doença de Hashimoto/patologia , Doença de Hashimoto/terapia , Humanos , Incidência , Iodeto Peroxidase/imunologia , Masculino , Fatores de Risco , Selênio/uso terapêutico , Tireoglobulina/imunologia , Testes de Função Tireóidea , Glândula Tireoide/patologia , Tireoidite Autoimune/tratamento farmacológico , Tireoidite Autoimune/epidemiologia , Tireoidite Autoimune/patologia , Tiroxina/uso terapêuticoRESUMO
PURPOSE: To evaluate how irradiation affects thyroid autoimmunity in mouse models of Hashimoto's thyroiditis and Graves' hyperthyroidism. MATERIALS AND METHODS: Non-obese diabetic (NOD)-H2(h4) mice spontaneously develop anti-thyroglobulin (Tg) antibodies and thyroiditis when supplied with sodium iodine (NaI) in the drinking water. BALB/c mice develop anti-thyrotropin receptor (TSHR) antibodies and hyperthyroidism following immunization with adenovirus expressing TSHR (Ad-TSHR). Mice were irradiated as follows: A single whole-body irradiation with 0.05, 0.5 or 3 Gy one week before or after the beginning of NaI or immunization with Ad-TSHR, fractionated whole-body irradiations with 0.05 Gy twice a week or 0.5 Gy once a week from one week before NaI or Ad-TSHR immunization, or a single regional irradiation to the thyroid gland with 0.5 Gy one week before NaI. The effect of a single irradiation with 0.05, 0.5 or 3 Gy on splenocytes was also evaluated. RESULTS: A single whole-body irradiation with 0.5 Gy one week before NaI exacerbated thyroiditis and increased anti-Tg antibody titers in NOD-H2(h4) mice. In contrast, any irradiation protocols employed did not affect incidence of hyperthyroidism or anti-TSHR antibody titers in BALB/c mice. High-dose irradiation increased the relative ratios of effector T cells to regulatory T cells (an indication of enhanced immune status) but kills most of T cells. CONCLUSIONS: These results indicate that a single whole-body low-dose irradiation with 0.5 Gy exacerbates thyroiditis in NOD-H2(h4) mice, data consistent with some clinical evidence for increased incidence of thyroid autoimmunity by environmental irradiation.
Assuntos
Antígenos H-2/imunologia , Doses de Radiação , Tireoidite Autoimune/patologia , Irradiação Corporal Total , Adenoviridae/genética , Animais , Anticorpos/imunologia , Modelos Animais de Doenças , Feminino , Regulação Viral da Expressão Gênica , Doença de Graves/imunologia , Doença de Graves/patologia , Doença de Hashimoto/induzido quimicamente , Doença de Hashimoto/imunologia , Doença de Hashimoto/patologia , Humanos , Imunização , Camundongos , Camundongos Endogâmicos NOD , Receptores da Tireotropina/imunologia , Receptores da Tireotropina/metabolismo , Linfócitos T/efeitos da radiação , Tireoidite Autoimune/imunologiaRESUMO
Turner's syndrome (TS) is a chromosomal disorder where phenotypic females have either a missing chromosome (45 X0) or a structural aberration of one of the chromosomes. It is possible for TS to accompany such autoimmune diseases as thyroid diseases, inflammatory intestinal diseases, diabetes mellitus, psoriatic arthritis and juvenile rheumatoid arthritis. Herein, we present an unusual case with Ankylosing spondylitis (AS) and autoimmune thyroiditis associated with TS. We suggest that the possibility that TS patients may also develop such other diseases as AS apart from the already known accompanying autoimmune diseases should not be ruled out when monitoring TS patients.
Assuntos
Espondilite Anquilosante/complicações , Tireoidite Autoimune/complicações , Síndrome de Turner/complicações , Adulto , Antirreumáticos/uso terapêutico , Cálcio/administração & dosagem , Terapia Combinada , Suplementos Nutricionais , Terapia por Exercício , Feminino , Humanos , Imageamento por Ressonância Magnética , Radiografia , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/patologia , Espondilite Anquilosante/patologia , Espondilite Anquilosante/terapia , Sulfassalazina/uso terapêutico , Tireoidite Autoimune/patologia , Síndrome de Turner/patologia , Vitamina D/administração & dosagemRESUMO
Autoimmune thyroiditis in humans has been linked to excess iodine intake. A causative relationship between dietary iodine and thyroiditis has been clearly established in animal models of thyroiditis, including the NOD.H2(h4) mouse strain, which develops enhanced thyroiditis spontaneously after supplementation of drinking water with sodium iodide. To assess the mechanisms by which iodine may contribute to disease pathogenesis, we have purified hypoiodinated thyroglobulin (Lo-I Tg) from the thyroids of mice fed methimazole and potassium perchlorate. This preparation contained only a trace of iodine and was poorly reactive to monoclonal antibody 42C3, which has been shown previously to distinguish hypoiodinated from normal Tg. A cloned T cell line 2D11 from a diseased NOD.H2(h4) mouse proliferated in response to normal Tg, but not to Lo-I Tg. Serum antibodies from NOD.H2(h4) mice with thyroiditis were poorly reactive to Lo-I Tg. To determine that these changes were due specifically to iodine content, Lo-I Tg was reiodinated in vitro. Reiodination of Lo-I Tg partially re-established the reactivity of NOD.H2(h4) serum antibodies. The data demonstrate that the reactivity of thyroglobulin-specific antibodies and certain T cells are dependent on the iodine content of thyroglobulin. These findings suggest that iodine contributes to autoimmune thyroiditis in the NOD.H2(h4) mouse by directly enhancing the antigenicity of thyroglobulin.
Assuntos
Iodo/imunologia , Tireoglobulina/imunologia , Tireoidite Autoimune/imunologia , Envelhecimento/imunologia , Animais , Autoanticorpos/imunologia , Linhagem Celular , Proliferação de Células , Camundongos , Camundongos Endogâmicos NOD , Índice de Gravidade de Doença , Linfócitos T/imunologia , Tireoidite Autoimune/patologiaRESUMO
Epidemiological studies, as well as animal models, indicate that iodine might be an immunogenic agent for the thyroid gland, at least in subjects predisposed to thyroid autoimmunity. This review presents data, either epidemiological or experimental, obtained in different conditions: constant and stable iodine status, either deficient, sufficient or excessive; long-term iodine prophylaxis; temporary supplementation with iodide (6-12 months) or iodised oil. Moreover, we also discuss data obtained in the general population, among subjects with euthyroid goiter, or autoimmune goiter, or even in women prone to post-partum thyroid diseases. It is concluded that the significant increase in the prevalence of autoimmune thyroid diseases in populations living in iodine sufficient areas should not prevent the implementation of the iodine prophylaxis.