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1.
Eur J Endocrinol ; 185(5): 743-753, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34524976

RESUMO

Objective: Genetic factors underpin the narrow intraindividual variability of thyroid function, although precise contributions of environmental vs genetic factors remain uncertain. We sought to clarify the heritability of thyroid function traits and thyroid peroxidase antibody (TPOAb) positivity and identify single nucleotide polymorphisms (SNPs) contributing to the trait variance. Methods: Heritability of thyroid-stimulating hormone (TSH), free T4 (fT4), free T3 (fT3) and TPOAb in a cohort of 2854 euthyroid, dizygous and monozygous twins (age range 11.9-16.9 years) from the Brisbane Longitudinal Twin Study (BLTS) was assessed using structural equation modelling. A genome-wide analysis was conducted on 2832 of these individuals across 7 522 526 SNPs as well as gene-based association analyses. Replication analysis of the association results was performed in the Raine Study (n = 1115) followed by meta-analysis to maximise power for discovery. Results: Heritability of thyroid function parameters in the BLTS was 70.8% (95% CI: 66.7-74.9%) for TSH, 67.5% (59.8-75.3%) for fT4, 59.7% (54.4-65.0%) for fT3 and 48.8% (40.6-56.9%) for TPOAb. The genome-wide association study (GWAS) in the discovery cohort identified a novel association between rs2026401 upstream of NCOA3 and TPOAb. GWAS meta-analysis found associations between TPOAb and rs445219, also near NCOA3, and fT3 and rs12687280 near SERPINA7. Gene-based association analysis highlighted SERPINA7 for fT3 and NPAS3 for fT4. Conclusion: Our findings resolve former contention regarding heritability estimates of thyroid function traits and TPOAb positivity. GWAS and gene-based association analysis identified variants accounting for a component of this heritability.


Assuntos
Estudo de Associação Genômica Ampla , Coativador 3 de Receptor Nuclear/genética , Testes de Função Tireóidea , Glândula Tireoide/fisiologia , Globulina de Ligação a Tiroxina/genética , Adolescente , Austrália/epidemiologia , Estudos de Coortes , Feminino , Humanos , Iodeto Peroxidase/análise , Iodeto Peroxidase/imunologia , Estudos Longitudinais , Masculino , Polimorfismo de Nucleotídeo Único , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Gêmeos Monozigóticos
2.
Medicine (Baltimore) ; 100(23): e26273, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115025

RESUMO

ABSTRACT: The association of nephropathy with autoimmune thyroid disease (AITD) has been reported previously. However, there is limited information on the relationship between thyroid autoantibodies and nephropathy. A retrospective study was conducted using the medical records of 246 patients with nephropathy, 82 of whom had concurrent AITD. General characteristics, thyroid function, autoantibodies, and the pathological types of nephropathy were analyzed. Immunohistochemistry was used to detect the thyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) in the kidneys. We found nephropathy patients with AITD exhibited higher serum levels of TPO-Ab, TG-Ab, thyroid-stimulating hormone receptor antibody (TR-Ab), and immunoglobulin G (IgG) (P < .05). Compared with the nephropathy without AITD group, the nephropathy with AITD group exhibited higher proportions of membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS), and relatively lower proportions of mesangial proliferative glomerulonephritis (MsPGN) and minimal change nephropathy (MCN) (P = .005). TPO-Ab and TG-Ab levels in the kidney were more prevalent in nephropathy patients with AITD than those without AITD (P = .015 and P = .026, respectively). Subgroup analysis demonstrated that serum levels of thyroid stimulating hormone (TSH), TG-Ab, TPO-Ab, immunoglobulin M (IgM), and IgG in the MN group were significantly higher, whereas the levels of free thyroxine (FT4) and estimated glomerular filtration rate (eGFR) were lower, as compared with MN with Hashimoto thyroiditis (HT) group (P < .05). TPO-Ab and TG-Ab expression levels in the kidneys were more prevalent in the MN group than in the MN with HT group (P = .034). The expression levels of FT4, TG-Ab, TPO-Ab, and thyroid-stimulating hormone receptor antibody (TSHR-Ab) in the serum were significantly higher in the MN group than in the MN with Graves disease (GD) group (P < .05). The expression of TPO-Ab in the kidneys was more prevalent in the MN group than in the MN with GD group (P = .011). In sum, the expressions of TPO-Ab and TG-Ab were more prevalent in the kidneys of patients with nephropathy and AITD. Our findings indicate that TPO-Ab and TG-Ab may play a role in the development of AITD-related nephropathy.


Assuntos
Autoanticorpos/análise , Glomerulonefrite Membranosa , Glomerulosclerose Segmentar e Focal , Doença de Hashimoto , Iodeto Peroxidase/imunologia , Receptores da Tireotropina/imunologia , Tireoglobulina/imunologia , Tireoidite Autoimune , Correlação de Dados , Feminino , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/patologia , Glomerulosclerose Segmentar e Focal/imunologia , Glomerulosclerose Segmentar e Focal/patologia , Doença de Hashimoto/sangue , Doença de Hashimoto/diagnóstico , Humanos , Imuno-Histoquímica , Rim/imunologia , Rim/patologia , Masculino , Pessoa de Meia-Idade , Testes de Função Tireóidea , Tireoidite Autoimune/sangue , Tireoidite Autoimune/diagnóstico , Tireoidite Autoimune/imunologia
4.
Biomed Pharmacother ; 140: 111733, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34029950

RESUMO

AIMS: This study aimed to investigate the therapeutic effect of Cordyceps sinensis-derived fungus Isaria felina on experimental autoimmune thyroiditis (EAT). METHODS: A NaI-induced EAT mouse model was established. The mice received oral administration of vehicle, low-dose Isaria felina (300 mg/kg), or high-dose Isaria felina (600 mg/kg) once a day for four weeks before euthanasia. Enzyme-linked immunosorbent assays (ELISA) was performed to measure serum thyroid-stimulating hormone (TSH) levels, thyroid antibodies, and cytokines. Hematoxylin and eosin (H&E) staining was conducted to assess histopathological changes in the thyroid tissue samples of mice. TUNEL and Bcl-2 immunohistochemistry (IHC) were performed to evaluate cell apoptosis, and cleaved caspase-3 IHC was performed to detect the relative expression in the thyroid tissue samples. RESULTS: Compared with KIO3 and KI water, NaI water consumption successfully induced EAT in mice, as evidenced by significantly increased circulating TSH and thyroid antibody levels, along with typical histopathological abnormalities of autoimmune thyroiditis (AIT) in the thyroid tissue samples. Compared with vehicle or low-dose Isaria felina, high-dose Isaria felina treatment resulted in significant reductions in white cell counts and circulating TSH, thyroid antibody, and cytokine levels of EAT mice. High-dose Isaria felina also alleviated histopathological abnormalities and attenuated TUNEL staining, Bcl-2 protein expression, and cleaved caspase-3 expression in the thyroid tissue samples. CONCLUSION: High-dose Isaria felina treatment alleviates thyroid inflammation and cell apoptosis in EAT, serving as a novel, promising therapeutic agent for AIT.


Assuntos
Beauveria , Tireoidite Autoimune/terapia , Animais , Autoanticorpos/sangue , Cordyceps , Modelos Animais de Doenças , Feminino , Iodeto Peroxidase/imunologia , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Glândula Tireoide/imunologia , Glândula Tireoide/patologia , Tireoidite Autoimune/sangue , Tireoidite Autoimune/imunologia , Tireotropina/sangue
5.
Front Immunol ; 12: 653356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796116

RESUMO

Background: Pemphigus is a rare but life-threatening autoimmune skin disease characterized by blistering on skin and/or mucous membranes. The physiological process of blister formation involves IgG antibodies against the desmogleins (Dsgs) and desmocollins (Dscs). Additional autoAbs have also been suggested to mediate the disease heterogeneity, such as anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies, the essential culprits of the immune system in autoimmune thyroid diseases. Purpose: To investigate the levels and antibody positivity of anti-TPO and anti-Tg antibodies in pemphigus patients. Methods: Antibody positivity and levels of anti-TPO and anti-Tg antibodies in pemphigus patients as compared to healthy controls were examined. A meta-analysis was conducted by reviewing six similar studies. Results: 98 Chinese pemphigus patients and 65 healthy controls were enrolled in the study. Our meta-analysis revealed a significant correlation between increased presence of positive anti-TPO and anti-Tg antibodies and pemphigus, particularly for pemphigus vulgaris (PV). Such correlation was also observed in our own hospitalized PV patients, but not in pemphigus foliaceus (PF) patients. In addition, the status of anti-TPO and anti-Tg antibodies were also compared between females and males within PV patients, PF patients or controls, as well as compared for females or males between pemphigus patients and controls. In the analysis of T cell counts, we found abnormal low CD3 + T cell counts (< 690 n/µl) were only detected in patients whose thyroid antibody levels were less than 20 IU/ml. Conclusion: Pemphigus patients showed higher levels and antibody positivity of anti-TPO and anti-Tg antibodies than healthy controls. Further investigations are needed to identify the pathogenic functions of these antibodies in pemphigus, as well as to identify the potential shared susceptibility genes.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Pênfigo/imunologia , Tireoglobulina/imunologia , Adulto , Idoso , Autoanticorpos/imunologia , Estudos de Casos e Controles , China , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Pênfigo/sangue , Estudos Retrospectivos , Adulto Jovem
6.
Nutrients ; 13(3)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33808030

RESUMO

Hashimoto's disease is listed among the most common endocrine causes of obesity. As treatment of obesity in women with Hashimoto's disease is frequently unsuccessful, the aim of this study was to evaluate the effectiveness of two different reducing diets and their influence on changes in thyroid parameters in female patients. A six-month observational/interventional study was performed on 100 women aged 18-65 years, previously diagnosed with Hashimoto's disease and obesity and receiving L-thyroxine. The women were randomly assigned to the test group (group A, n = 50) following elimination/reducing diets, and the control group (group B, n = 50) following reducing diets with the same caloric content (without elimination). Anthropometric and thyroid parameters were evaluated at the beginning, after 3 months and after 6 months of treatment. In both groups a significant decrease in BMI and body fat percentage was achieved, but in test group A the decrease in BMI and body fat percentage was significantly greater than in control group B (p < 0.002 and p = 0.026, respectively). Serum TSH (thyroid stimulating hormon) levels decreased significantly more in group A than in group B (p < 0.001). Group A exhibited significantly greater increases in fT4 and fT3 levels than the control group (p < 0.001) as well as significantly greater decreases in the levels anti-TPO (thyroid peroxidase) (p < 0.001) and anti-TG (thyreoglobulin) antibodies (p = 0.048). The application of reducing diets with product elimination was found to be a more beneficial tool for changing anthropometric and thyroid parameters in women suffering from obesity and Hashimoto's disease than classic reducing diets with the same energy values and macronutrient content.


Assuntos
Dieta Redutora/métodos , Doença de Hashimoto/dietoterapia , Obesidade/dietoterapia , Tecido Adiposo , Adolescente , Adulto , Idoso , Antropometria , Autoanticorpos/sangue , Autoantígenos/imunologia , Índice de Massa Corporal , Feminino , Doença de Hashimoto/sangue , Doença de Hashimoto/imunologia , Humanos , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/imunologia , Tireoglobulina/imunologia , Testes de Função Tireóidea , Glândula Tireoide/imunologia , Tireotropina/sangue , Tiroxina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
7.
J Med Case Rep ; 15(1): 108, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33653380

RESUMO

BACKGROUND: Hypothyroidism is diagnosed on the basis of laboratory tests because of the lack of specificity of the typical clinical manifestations. There is conflicting evidence on screening for hypothyroidism. CASE PRESENTATION: We report a case of an apparently healthy 19-year-old Kuwaiti woman referred to our clinic with an incidental finding of extremely high thyroid-stimulating hormone (TSH), tested at the patient's insistence as she had a strong family history of hypothyroidism. Despite no stated complaints, the patient presented typical symptoms and signs of hypothyroidism on evaluation. Thyroid function testing was repeated by using different assays, with similar results; ultrasound imaging of the thyroid showed a typical picture of thyroiditis. Treatment with levothyroxine alleviated symptoms and the patient later became biochemically euthyroid on treatment. CONCLUSION: There is controversy regarding screening asymptomatic individuals for hypothyroidism; therefore, it is important to maintain a high index of suspicion when presented with mild signs and symptoms of hypothyroidism especially with certain ethnic groups, as they may be free of the classical symptoms of disease.


Assuntos
Hipotireoidismo/diagnóstico , Tireoidite Autoimune/diagnóstico , Alopecia/fisiopatologia , Apetite , Autoanticorpos/imunologia , Constipação Intestinal/fisiopatologia , Depressão/fisiopatologia , Fadiga/fisiopatologia , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/fisiopatologia , Achados Incidentais , Iodeto Peroxidase/imunologia , Menorragia/fisiopatologia , Índice de Gravidade de Doença , Glândula Tireoide/diagnóstico por imagem , Tireoidite Autoimune/sangue , Tireoidite Autoimune/imunologia , Tireoidite Autoimune/fisiopatologia , Tireotropina/sangue , Tiroxina/sangue , Tiroxina/uso terapêutico , Ultrassonografia , Ganho de Peso , Adulto Jovem
8.
BMC Pregnancy Childbirth ; 21(1): 136, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588796

RESUMO

BACKGROUND: Autoimmunity increases with age and is often commonly evaluated in women of the reproductive age group. Prevalence of thyroid antibodies is common even in euthyroid pregnant women. We aim to compare the association of thyroid antibody status on the maternal and neonatal outcomes in pregnant women with hypothyroidism. METHODS: We conducted a cross-sectional retrospective study on 718 cases in the Aga Khan University Hospital. Information was collected on pregnant women who have been diagnosed with hypothyroidism before conception or during their antenatal period. Laboratory data were recorded for thyroid peroxidase antibodies, anti-thyroglobulin antibodies, and thyroid-stimulating hormone levels. Maternal and neonatal outcomes were also noted from medical file records. Data analysis was performed on Statistical Package for the Social Sciences version 20.0. RESULTS: Overall, 146 out 718 cases were included for final analysis. Thyroid peroxidase antibodies were positive in 66.4% and anti-thyroglobulin was positive in 52.1% cases, whereas 43.8% of cases had both antibodies positive. Pre-gestational diabetes was significantly associated with thyroid autoimmunity. There was a 73% less chance of gestational hypertension for thyroid autoimmune groups. Gestational diabetes and maternal (chronic) hypertension were found to have an independent effect on postpartum hemorrhage. Hypertensive disorders in pregnancy were found to have an independent risk for premature birth. CONCLUSION: Our study reports a 74.7% prevalence of positive thyroid antibodies in hypothyroid pregnant women, with higher association with pre-gestational diabetes. Gestational hypertension was least likely to occur in thyroid autoimmune groups. None of the outcomes were independently associated with worse outcomes.


Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Hipotireoidismo/imunologia , Iodeto Peroxidase/imunologia , Complicações na Gravidez/imunologia , Resultado da Gravidez/epidemiologia , Aborto Espontâneo/epidemiologia , Descolamento Prematuro da Placenta/epidemiologia , Adulto , Índice de Apgar , Doenças Autoimunes/tratamento farmacológico , Cesárea/estatística & dados numéricos , Feminino , Macrossomia Fetal/epidemiologia , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Hipotireoidismo/tratamento farmacológico , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Icterícia Neonatal/epidemiologia , Masculino , Hemorragia Pós-Parto/epidemiologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Gravidez em Diabéticas/epidemiologia , Nascimento Prematuro/epidemiologia , Natimorto/epidemiologia , Nascimento a Termo , Tireotropina/sangue , Tiroxina/uso terapêutico , Adulto Jovem
9.
Endocr Regul ; 55(1): 5-15, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33600668

RESUMO

Objective. Thyroid hormones play an important role in the development and maturation of the central nervous symptom and their failure in the prenatal period leading to an irreversible brain damage. Their effect on the brain of adult, however, has not been fully studied. With the discovery of neurogenesis in the adult brain, many recent studies have been focused on the understanding the basic mechanisms controlling this process. Many neurogenesis regulatory genes are not only transcribed but also translated into the blood cells. The goal of our study was to analyze the transcriptional activity of neurogenesis regulatory genes in peripheral blood cells in patients with thyroid pathology.Methods. The pathway-specific PCR array (Neurotrophins and Receptors RT2 Profiler PCR Array, QIAGEN, Germany) was used to identify and validate the neurogenesis regulatory genes expression in patients with thyroid pathology and control group.Results. The results showed that GFRA3, NGFR, NRG1, NTF3, NTRK1, and NTRK2 significantly decreased their expression in patients with autoimmune thyroiditis with rising serum of autoantibodies. The patients with primary hypothyroidism, as a result of autoimmune thyroiditis and postoperative hypothyroidism, had significantly lower expression of FGF2, NGFR, NRG1, and NTF3. The mRNA level of CNTFR was markedly decreased in the group of patients with postoperative hypothyroidism. No change in the ARTN, PSPN, TFG, MT3, and NELL1 expression was observed in any group of patients.Conclusion. The finding indicates that a decrease in thyroid hormones and a high level of autoantibodies, such as anti-thyroglobulin antibody and anti-thyroid peroxidase antibody, affect the expression of mRNA neurogenesis-regulated genes in patients with thyroid pathology.


Assuntos
Regulação da Expressão Gênica/fisiologia , Hipotireoidismo/genética , Hipotireoidismo/metabolismo , Neurogênese/genética , Tireoidite Autoimune/genética , Tireoidite Autoimune/imunologia , Adulto , Autoanticorpos/sangue , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipotireoidismo/imunologia , Iodeto Peroxidase/imunologia , Pessoa de Meia-Idade , Fatores de Crescimento Neural/genética , RNA Mensageiro/análise , Hormônios Tireóideos/sangue , Hormônios Tireóideos/fisiologia
10.
Am J Gastroenterol ; 116(5): 1015-1023, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33009065

RESUMO

INTRODUCTION: Nonceliac wheat sensitivity (NCWS) is characterized by intestinal and extraintestinal manifestations consequent to wheat ingestion in subjects without celiac disease and wheat allergy. Few studies investigated the relationship between NCWS and autoimmunity. The aim of this study is to evaluate the frequency of autoimmune diseases (ADs) and autoantibodies in patients with NCWS. METHODS: Ninety-one patients (13 men and 78 women; mean age of 40.9 years) with NCWS, recruited in a single center, were included. Seventy-six healthy blood donors (HBD) and 55 patients with a diagnosis of irritable bowel syndrome (IBS) unrelated to NCWS served as controls. Autoantibodies levels were measured. Human leukocyte antigen haplotypes were determined, and duodenal histology performed in all patients carrying the DQ2/DQ8 haplotypes. Participants completed a questionnaire, and their medical records were reviewed to identify those with ADs. RESULTS: Twenty-three patients with NCWS (25.3%) presented with ADs; autoimmune thyroiditis (16 patients, 17.6%) was the most frequent. The frequency of ADs was higher in patients with NCWS than in HBD (P = 0.002) and in patients with IBS (P = 0.05). In the NCWS group, antinuclear antibodies tested positive in 71.4% vs HBD 19.7%, and vs patients with IBS 21.8% (P < 0.0001 for both). The frequency of extractable nuclear antigen antibody (ENA) positivity was significantly higher in patients with NCWS (21.9%) than in HBD (0%) and patients with IBS (3.6%) (P = 0.0001 and P = 0.004, respectively). Among the patients with NCWS, 9.9% tested positive for antithyroglobulin, 16.5% for antithyroid peroxidase, and 14.3% for antiparietal cell antibodies; frequencies were not statistically different from controls. The presence of ADs was related to older age at NCWS diagnosis, female sex, duodenal lymphocytosis, and eosinophil infiltration. DISCUSSION: One in 4 patients with NCWS suffered from AD, and serum antinuclear antibodies were positive in a very high percentage of cases. These data led us to consider NCWS to be associated to ADs.


Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Hipersensibilidade a Trigo/imunologia , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Feminino , Haplótipos , Humanos , Iodeto Peroxidase/imunologia , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais , Inquéritos e Questionários , Hipersensibilidade a Trigo/dietoterapia
11.
F1000Res ; 9: 337, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33299547

RESUMO

Background: Validated biomarkers are needed to identify patients at increased risk of immune-related adverse events (irAEs) to immune checkpoint blockade (ICB). Antibodies directed against endogenous antigens can change after exposure to ICB. Methods: Patients with different solid tumors stratified into cohorts received pembrolizumab every 3 weeks in a Phase II trial (INSPIRE study). Blood samples were collected prior to first pembrolizumab exposure (baseline) and approximately 7 weeks (pre-cycle 3) into treatment. In a discovery analysis, autoantibody target immuno-mass spectrometry was performed in baseline and pre-cycle 3 pooled sera of 24 INSPIRE patients based on clinical benefit (CBR) and irAEs. Results: Thyroglobulin (Tg) and thyroid peroxidase (TPO) were identified as the candidate autoantibody targets. In the overall cohort of 78 patients, the frequency of CBR and irAEs from pembrolizumab was 31% and 24%, respectively. Patients with an anti-Tg titer increase ≥1.5x from baseline to pre-cycle 3 were more likely to have irAEs relative to patients without this increase in unadjusted, cohort adjusted, and multivariable models (OR=17.4, 95% CI 1.8-173.8, p=0.015). Similarly, patients with an anti-TPO titer ≥ 1.5x from baseline to pre-cycle 3 were more likely to have irAEs relative to patients without the increase in unadjusted and cohort adjusted (OR=6.1, 95% CI 1.1-32.7, p=0.035) models. Further, the cohort adjusted analysis showed patients with anti-Tg titer greater than median (10.0 IU/mL) at pre-cycle 3 were more likely to have irAEs (OR=4.7, 95% CI 1.2-17.8, p=0.024). Patients with pre-cycle 3 anti-TPO titers greater than median (10.0 IU/mL) had a significant difference in overall survival (23.8 vs 11.5 months; HR=1.8, 95% CI 1.0-3.2, p=0.05). Conclusions: Patient increase ≥1.5x of anti-Tg and anti-TPO titers from baseline to pre-cycle 3 were associated with irAEs from pembrolizumab, and patients with elevated pre-cycle 3 anti-TPO titers had an improvement in overall survival.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Autoanticorpos/sangue , Iodeto Peroxidase/imunologia , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Tireoglobulina/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores/sangue , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Adulto Jovem
12.
Int J Mol Sci ; 21(19)2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33023043

RESUMO

In some instances, when chemicals bind to proteins, they have the potential to induce a conformational change in the macromolecule that may misfold in such a way that makes it similar to the various target sites or act as a neoantigen without conformational change. Cross-reactivity then can occur if epitopes of the protein share surface topology to similar binding sites. Alteration of peptides that share topological equivalence with alternating side chains can lead to the formation of binding surfaces that may mimic the antigenic structure of a variant peptide or protein. We investigated how antibodies made against thyroid target sites may bind to various chemical-albumin compounds where binding of the chemical has induced human serum albumin (HSA) misfolding. We found that specific monoclonal or polyclonal antibodies developed against thyroid-stimulating hormone (TSH) receptor, 5'-deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin (TBG), thyroxine (T4), and triiodothyronine (T3) bound to various chemical HSA compounds. Our study identified a new mechanism through which chemicals bound to circulating serum proteins lead to structural protein misfolding that creates neoantigens, resulting in the development of antibodies that bind to key target proteins of the thyroid axis through protein misfolding. For demonstration of specificity of thyroid antibody binding to various haptenic chemicals bound to HSA, both serial dilution and inhibition studies were performed and proportioned to the dilution. A significant decline in these reactions was observed. This laboratory analysis of immune reactivity between thyroid target sites and chemicals bound to HSA antibodies identifies a new mechanism by which chemicals can disrupt thyroid function.


Assuntos
Anticorpos/imunologia , Proteínas Sanguíneas/imunologia , Haptenos/imunologia , Albumina Sérica Humana/imunologia , Anticorpos/genética , Especificidade de Anticorpos/imunologia , Proteínas Sanguíneas/química , Epitopos/imunologia , Haptenos/genética , Humanos , Iodeto Peroxidase/genética , Iodeto Peroxidase/imunologia , Ligação Proteica/imunologia , Receptores da Tireotropina/genética , Receptores da Tireotropina/imunologia , Albumina Sérica Humana/química , Glândula Tireoide/imunologia , Tri-Iodotironina/genética , Tri-Iodotironina/imunologia
13.
PLoS One ; 15(10): e0240198, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33007021

RESUMO

Hypertension frequently occurs in subclinical hypothyroidism (SCH). By bolstering thyroid inflammation, anti-peroxidase antibody (TPO-Ab) causes autoimmune thyroiditis, which is one of the most common causes of SCH. Since the absence of thyroid cysts is associated with TPO-Ab (+) based on the indication of latent thyroid damage, we explored the potential mechanism underlying the association among TPO-Ab, SCH, hypertension, and thyroid cysts. A cross-sectional study of 1,483 Japanese aged 40-74 years was conducted. Thyroid cysts were defined as those having a maximum diameter of ≥ 2.0 mm, containing no solid component. TPO-Ab (+) was positively associated with SCH with hypertension (adjusted odds ratio [OR] and 95% confidence interval [CI], 2.62 [1.40, 4.89]) but not with SCH without hypertension (0.84 [0.37, 1.89]), respectively. Moreover, among participants without thyroid cysts, SCH was positively associated with hypertension (2.15 [1.23, 3.76]) but not among participants with thyroid cysts (0.58 [0.16, 2.16]), respectively. TPO-Ab was positively associated with SCH with hypertension, but not with SCH without hypertension. In addition, status of thyroid cysts might act as a determinant factor on the association between SCH and hypertension. These findings are efficient tools to clarify the background mechanism that underlies SCH.


Assuntos
Cistos/imunologia , Hipertensão/imunologia , Hipotireoidismo/imunologia , Iodeto Peroxidase/imunologia , Doenças da Glândula Tireoide/imunologia , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Autoanticorpos/imunologia , Estudos Transversais , Feminino , Humanos , Hipertensão/complicações , Hipotireoidismo/complicações , Hipotireoidismo/enzimologia , Masculino , Pessoa de Meia-Idade , Doenças da Glândula Tireoide/complicações
14.
Medicine (Baltimore) ; 99(38): e22214, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957357

RESUMO

Anti-thyroid peroxidase antibody (TPO-Ab), which is the known cause of autoimmune thyroid disease, enhances proinflammatory cytokine responses. Since low-grade inflammation is a known risk factor for atherosclerosis, a normal range of TPO-Ab (TPO-Ab negative) could be positively associated with atherosclerosis among participants with normal thyroid function. However, no study reported the association between normal range of TPO-Ab and atherosclerosis among eu-thyroid participants. A cross-sectional study was conducted with 1165 Japanese individuals with normal thyroid function (ie, normal range of free triiodothyronine [free T3] and free thyroxine [free T4]), aged 40 to 74 years, who participated in an annual health checkup in 2014. Among the study population, 115 were diagnosed as having atherosclerosis. A normal range value of TPO-Ab titer is revealed to be positively associated with atherosclerosis; sex, age, thyroid function (free T3 and thyroid-stimulating hormone), and known cardiovascular risk factor adjusted odds ratio and 95% confidence interval of atherosclerosis for logarithmic values of TPO-Ab was 2.23 (1.11, 4.47). When we limited the analysis to participants with normal levels of thyroid-stimulating hormone, this association became slightly stronger (2.65 [1.27,5.51]). Among the eu-thyroid general population, a normal range of TPO-Ab titer is revealed to be positively associated with atherosclerosis. Even though a TPO-Ab titer is not clinically relevant and is not associated with autoimmune thyroid disease, it could influence endothelial remodeling including atherosclerosis.


Assuntos
Aterosclerose/sangue , Autoanticorpos/sangue , Iodeto Peroxidase/imunologia , Idoso , Grupo com Ancestrais do Continente Asiático , Aterosclerose/imunologia , Autoanticorpos/imunologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Tireotropina/sangue
15.
Fertil Steril ; 114(6): 1306-1314, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32912635

RESUMO

OBJECTIVE: To investigate whether levothyroxine is associated with improved live birth and other benefits in women with thyroid autoimmunity. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women positive for thyroid peroxidase antibody. INTERVENTION(S): MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched without any language restrictions. Pooled effect sizes were calculated using random-effects models. MAIN OUTCOME MEASURE(S): The primary outcome was the incidence of live birth, miscarriage, preterm birth, clinical pregnancy, ectopic pregnancy, neonatal admission, and birth weight. The summary measures were reported as relative risk (RR) with 95% confidence interval. RESULT(S): Levothyroxine supplementation was not associated with an increased rate of live birth or a decreased risk of miscarriage. Results were similar in subgroup analyses of live birth by age, baseline thyrotropin, baseline thyroid peroxidase antibody, body mass index, and use of assisted conception. For live birth, the effect estimate lay within the futility boundary for RR of 20% and 15%, but at a 10% RR, the effect estimate lay between the futility boundary and the inferior boundary. CONCLUSION(S): High- to moderate-quality evidence demonstrated that the use of levothyroxine was not associated with improvements in clinical pregnancy outcomes among women positive for thyroid peroxidase antibody. REGISTRATION NUMBER: PROSPERO CRD42019132976.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Doenças Autoimunes/tratamento farmacológico , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Complicações na Gravidez/etiologia , Doenças da Glândula Tireoide/tratamento farmacológico , Tiroxina/uso terapêutico , Adulto , Doenças Autoimunes/sangue , Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Biomarcadores/sangue , Peso ao Nascer , Feminino , Humanos , Recém-Nascido , Nascido Vivo , Gravidez , Complicações na Gravidez/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/imunologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-32849259

RESUMO

Objective: It has been shown that women with polycystic ovary syndrome (PCOS), as well as Hashimoto's thyroiditis (HT), are characterized by increased incidence of infertility. Serum anti-Müllerian hormone (AMH), which reflects ovarian reserve, is elevated in PCOS women and is decreased in women with HT. The Rotterdam criteria recognize four clinical PCOS phenotypes, i.e., phenotypes A, B, C, and D. The aim of the present study was to investigate the relation between serum concentrations of thyroid peroxidase antibodies (TPOAbs) and ovarian reserve in different PCOS phenotypes. Patients and methods: We examined 141 women with PCOS [phenotype A was diagnosed in 67 (47.5%) women, phenotype B in 30 (21.3%), phenotype C in 28 (19.9%), and phenotype D in 16 (11.3%)] and 88 control subjects of similar age; all women were euthyroid. Serum concentrations of AMH, thyroid-stimulating hormone (TSH), thyroid hormones, and TPOAbs were assessed. Results: We observed positive serum TPOAbs in 21.9% women with PCOS and in 23.9% controls (p = 0.07). We did not find differences in the frequency of detection of positive serum TPOAbs between phenotypes A, B, and C and the control group (p > 0.05). We did not observe a difference in AMH levels between TPOAbs-positive and TPOAbs-negative women, both in the control group and the PCOS women (all p > 0.05). However, serum AMH concentration was markedly higher in the whole PCOS group (p < 0.01) and in phenotype A (p < 0.01) vs. controls when the serum concentration of TPOAbs was negative. In the groups with positive serum levels of TPOAbs, serum concentration of AMH did not differ between PCOS phenotypes and controls (p = 0.23). Additionally, we observed that serum AMH concentration was related to the level of TPOAbs in the PCOS group (r = -0.4, p = 0.02). Conclusions: The frequency of serum detection of positive TPOAbs did not differ between PCOS phenotypes with clinical/biochemical hyperandrogenism and the control group. The observation of the difference in serum AMH between the PCOS and control groups only in TPOAbs negative women together with the inverse relation of TPOAbs with serum AMH only in the PCOS group might suggest that ovarian reserve is influenced by TPOAbs in PCOS.


Assuntos
Autoanticorpos/sangue , Iodeto Peroxidase/imunologia , Reserva Ovariana , Síndrome do Ovário Policístico/patologia , Glândula Tireoide/patologia , Adulto , Autoanticorpos/imunologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Fenótipo , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/imunologia , Estudos Prospectivos , Glândula Tireoide/imunologia , Glândula Tireoide/metabolismo , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-32849304

RESUMO

Background: Antithyroperoxidase (TPOAb) and antithyroglobulin (TgAb) antibodies are associated with abnormal thyrotropin (TSH) levels. However, the effect of dynamic changes in TPOAb and TgAb on incident abnormal TSH is unknown. Methods: A total of 2,387 euthyroid participants aged 18 years or older from three rural areas in northern China were enrolled in this cohort study. Questionnaire interviews and laboratory measurements were performed at baseline in 1999 and at follow-up in 2004. Multinomial logistic regression was used to examine the relationship between changes in thyroid antibodies and incident abnormal TSH levels. Results: In this 5 year follow-up study, TPOAb tier gain was significantly associated with an increased risk of subnormal TSH levels (adjusted RR, 1.535; 95% CI: 1.357-1.736) and supranormal TSH levels (adjusted RR, 1.378; 95% CI: 1.196-1.587), and TgAb tier gain was significantly associated with an increased risk of supranormal (adjusted RR, 1.090; 95% CI: 1.007-1.179) TSH levels. Both thyroid antibody-positive seroconversion and persistent positivity were significantly associated with an increased risk of incident abnormal TSH levels. Thyroid antibody positive seroconversion was associated with a higher risk of incident subnormal TSH than incident supranormal TSH, whereas persistent positive thyroid antibody was associated with a higher risk of incident supranormal TSH than incident subnormal TSH. Conclusions: Dynamic thyroid antibody changes may be related to incident abnormal TSH levels. Those with persistent positive thyroid antibody were more likely to have supranormal TSH than subnormal TSH, and those with positive seroconversion were more likely to have subnormal TSH than supranormal TSH. Further studies are needed to confirm this conclusion and to explore this association mediated by TSH receptor antibodies.


Assuntos
Autoanticorpos/sangue , Biomarcadores/sangue , Iodeto Peroxidase/imunologia , Doenças da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/imunologia , Adulto Jovem
18.
J Physiol Anthropol ; 39(1): 16, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678000

RESUMO

BACKGROUND: The prevalence of allergic and autoimmune conditions has been steadily increasing in wealthy nations over the past century. One hypothesis put forward to explain this is the Old Friends Hypothesis, which posits that increased hygiene, urbanization, and lifestyle changes have reduced our exposure to parasites and microbes that we co-evolved with, resulting in immune dysregulation. However, research in traditionally living populations, who are exposed to greater parasite and pathogen loads such as those encountered during our evolution, is limited, in part due to a lack of minimally invasive, field-friendly biomarkers of autoimmune disorders. We therefore developed an ELISA to assess positivity for thyroid peroxidase autoantibody (TPO-Ab), an indicator of autoimmune thyroid disease, based on dried blood spot (DBS) samples. RESULTS: We used the Accubind anti-thyroid peroxidase test system to screen our validation samples comprising matched fingerprick DBS, venous DBS, and plasma samples from 182 adults. After confirming that we had TPO-Ab-positive individuals in our validation sample (n = 12), we developed an indirect ELISA to measure TPO-Ab levels from one 3-mm DBS punch. The sensitivity and specificity of our assay for DBS samples ranged from 91.7-100% and 98.2-98.8%, respectively, using a cut-off value of ≥ 26 IU/mL. Intra-assay reliability for duplicate quality control DBS punches was 5.2%, while inter-assay reliability ranged from 11.5-24.4% for high, medium, and low DBS controls. Dilutional linearity ranged from 80 to 120%, and spike and recovery experiments indicated that the DBS matrix does not interfere with the detection of TPO-Ab. TPO-Ab levels remained stable in DBS samples stored at - 28 °C or - 80 °C, but decreased over time in DBS samples kept at 22 °C or at 37 °C. CONCLUSIONS: We developed an in-house, kit-independent indirect ELISA assay to determine individuals' TPO-Ab positivity based on dried blood spots, representing a cost-effective method with potential applications in a range of research settings.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Teste em Amostras de Sangue Seco/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Doenças da Glândula Tireoide/diagnóstico , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
19.
Croat Med J ; 61(3): 230-238, 2020 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-32643339

RESUMO

AIM: To analyze the association of thyroid function and hormone levels with metabolic syndrome (MetS) and its components. METHODS: This cross-sectional population-based study involved 2183 Croatian individuals with no history of thyroid disease, hypertension, diabetes, and hyperlipidemia. MetS was diagnosed according to the National Cholesterol Education Program's Adult Treatment Panel III criteria. RESULTS: We found no association between thyroid function groups and the prevalence of MetS and its components. Clinically hypothyroid participants showed significantly higher triceps skinfold measurements than subclinically hypothyroid and euthyroid participants. Furthermore, clinically hypothyroid participants had higher abdominal skinfold thickness than subclinically hypothyroid participants. Otherwise, suprailiac and abdominal skinfold measurements were higher in the subclinically and clinically hyperthyroid group of participants compared with euthyroid and subclinically hypothyroid participants. A strong positive association of thyroid-stimulating hormone (TSH) and strong negative association of free triiodothyronine (fT3) and free thyroxine (fT4) levels with HOMA-IR and cholesterol levels were found. Furthermore, the fT4 level also showed a strong negative association with HDL and triceps skinfold thickness. CONCLUSIONS: This study supports the standing that TSH, fT3, and fT4 levels are important variables to determine the association of thyroid function with MetS.


Assuntos
Síndrome Metabólica/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Autoantígenos/imunologia , Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Tireoglobulina/imunologia , Hormônios Tireóideos/sangue , Adulto Jovem
20.
PLoS One ; 15(6): e0233957, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555697

RESUMO

INTRODUCTION: Autoantibodies (autoAbs) against desmoglein-1 (DSG1) and desmoglein-3 (DSG3) have conventionally been studied and well accepted in the pathogenesis of pemphigus vulgaris (PV) and foliaceus (PF). Recent studies have suggested that non-DSG autoAbs may contribute to the pathogenesis of pemphigus, including autoAbs directed at acetylcholine receptors (AChR) and thyroid peroxidase (TPO). The purpose of this study is to retrospectively analyze PV and PF patient sera to better understand the relationship between anti-AChR and -TPO Abs to disease activity and DSG reactivity between patients treated with prednisone and steroid sparing agents (SSA; n = 22) or prednisone and rituximab (n = 21). METHODS: Patients were evaluated at 2 time points, T1 and T2, for disease activity using the Pemphigus Disease Area Index (PDAI), and sera were tested for the presence of TPO, DSG1, DSG3, muscarinic (M3) and nicotinic (n) AChR IgG autoAbs, as well as antibodies against Varicella Zoster Virus (VZV) by ELISA. RESULTS: Disease activity significantly decreased in patients from T1 to T2 (p < .0001). A significant difference was seen in IgG anti-DSG1 (p < .0001) and anti-DSG3 (p = .0049) levels when T1 was compared to T2 in both treatment groups. A significant increase was found between pemphigus patients and normal subjects with nAChR (p < .0001) at T1 but not with m3AChR, TPO or VZV Abs. No significant difference was seen between T1 and T2 values in patients with pemphigus for the non-desmoglein Abs TPO (p = .7559), M3AChR (p = .9003), nAChR (p = .5143) or VZV (p = .2454). These findings demonstrate that although an increase in IgG anti-nAChR autoAbs was found in PV and PF subjects, these Abs did not decrease with treatment. No other non-DSG Abs were increased or significantly changed over time in patients with pemphigus. This suggests that anti -AChR and -TPO Abs may not play a direct role in the pathogenesis of most patients with pemphigus, but does not rule out a role for non-DSG auto antibodies in distinct subsets of pemphigus patient.


Assuntos
Autoanticorpos/sangue , Desmogleína 1/imunologia , Desmogleína 3/imunologia , Imunoglobulina G/sangue , Pênfigo/imunologia , Receptor Muscarínico M3/imunologia , Receptores Nicotínicos/imunologia , Adulto , Idoso , Autoantígenos/imunologia , Feminino , Humanos , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Masculino , Pessoa de Meia-Idade , Pênfigo/tratamento farmacológico , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab/uso terapêutico , Adulto Jovem
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