Effect of Buzhong Yiqitang on Th17/Treg Immune Imbalance and Notch1 Signaling Pathway in AIT Mice / 中国实验方剂学杂志

ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 （Th17）/regulatory T cell （Treg） and Notch1 signaling pathway in mice with autoimmune thyroiditis （AIT）. MethodA total of 60 8-week-old NOD.H-2h4 mice were randomly divided into the normal group， model group， western medicine group （selenium yeast tablet， 32.5 mg·kg-1）， and low-dose （4.78 g·kg-1·d-1）， middle-dose （9.56 g·kg-1·d-1）， and high-dose （19 g·kg-1·d-1） Buzhong Yiqitang groups， with 10 mice in each group. The normal group was fed with distilled water， and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously， the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies （TGAb）， thyroid-stimulating hormone （TSH）， free triiodothyronine （FT3）， and free thyroid hormone （FT4） were detected by enzyme-linked immunosorbent assay （ELISA）， and thyroid tissue changes were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt （RORγt）， interleukin （IL）-17， forkhead box P3 （FoxP3）， IL-10， Notch1， and hair division-related enhancer 1 （Hes1） in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the normal group， the thyroid structure of the model group was severely damaged， and lymphocytes were infiltrated obviously. The levels of serum TGAb， FT3， and FT4 contents were significantly increased， and TSH content was significantly decreased （P<0.01）. The mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were significantly increased， while those of FoxP3 and IL10 were significantly decreased in the model group （P<0.01）. Compared with the model group， thyroid structural damage and lymphocyte infiltration were improved in the treatment groups， and serum TGAb， FT3， and FT4 contents were significantly decreased. TSH content was increased， and mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees （P<0.05， P<0.01）， and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice， and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.

Ovarian reserve in adolescent girls with autoimmune thyroiditis

ABSTRACT Objectives: To assess serum anti-Müllerian hormone (AMH) levels as an ovarian reserve marker in adolescent girls with autoimmune thyroiditis (AIT) and explore the relationship of this marker with autoimmunity and thyroid function biomarkers. Subjects and methods: This study included 96 adolescent girls with newly diagnosed AIT and 96 healthy, age- and sex-matched controls. All participants were evaluated with detailed history taking and physical examination, thyroid ultrasound, and measurement of levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), antithyroid peroxidase antibodies (TPOAb), antithyroglobulin antibody (TGAb), estradiol, total testosterone, and anti-Müllerian hormone (AMH) levels. The LH/FSH ratio was also calculated. Among 96 patients evaluated, 78 were overtly hypothyroid and 18 were euthyroid. AMH levels were significantly lower in participants with overt hypothyroidism and euthyroidism compared with controls. Results: Serum levels of AMH correlated negatively with age, body mass index (BMI) standard deviation score (SDS), and TPOAb, TGAb, and TSH levels but positively with FT4 levels. In multivariate analysis, AMH levels correlated significantly with age (odds ratio [OR] = 1.65, 95% confidence interval [CI] 1.18-2.32, p = 0.05), BMI SDS (OR = 2.3, 95% CI, 2.23-3.50, p = 0.01), TSH (OR = 2.43, 95% CI 1.5-2.8, p = 0.01), and TPOAb (OR = 4.1, 95% CI 3.26-8.75, p = 0.001). Conclusions: Ovarian reserve of adolescent girls with AIT, as measured by serum AMH levels, is affected by thyroid autoimmunity and hypothyroidism, indicating a possible need for ovarian reserve monitoring in these patients.

Case-control study of risk factors for autoimmune thyroiditis in adults in the Xindu region / 公共卫生与预防医学

Objective To explore the influencing factors of autoimmune thyroid disease in Xindu region and provide a basis for preventing the occurrence of autoimmune thyroiditis.Methods Using case-control study, 581 autoimmune thyroid patients treated in 2016-2020 in Chengdu Xindu District Hospital of 2020, and 450 healthy patients were selected as the control group. Relevant data were obtained and the influencing factors of adult autoimmune thyroid disease were analyzed by univariate and multivariate logistic regression model. Results Univariate results showed that the observed BMI of 30.0 kg/m2, hyperlipidemia, metabolic syndrome and urinary iodine ( 200 μg/L) were higher than control group, with thyroid function [free triiodinated thyrigenine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH)), autothyroid antibody [thyroglobulin antibody (TGAb), antithyroid peroxidase antibody (TPOAb),] greater than control group (P <0.05).According to logistic regression analysis, body mass index 30.0, TGAb positive, TPOAb positive, hyperlipidemia, and metabolic syndrome were independent risk factors for adult autoimmune thyroiditis [OR (95% CI): 1.965 (1.340), 3.1262 (1.568-8.243), 3.089 (1.753-7.166), 2.507 (1.164 -4.956), 2.218 (1.207 -3.362), P <0.05]. Conclusion Body mass index of 30.0 kg/m2, hyperlipidemia and metabolic syndrome are the risk factors for adult autoimmune thyroiditis in Xindu region.Controlling weight, controlling autoimmune thyroiditis and metabolic syndrome are the key to reducing adult autoimmune thyroiditis in Xindu region.

Correlation of neutrophil extracellular traps with T cells differentiation in Hashimoto′s thyroiditis mice and vitamin D′s relief effect / 中华内分泌代谢杂志

Objective:To investigate correlation between neutrophil extracellular traps(NETs) formation and T cell subsets in mice with experimental autoimmune thyroiditis(EAT) and the impact of active vitamin D intervention.Methods:Six-week-old female BALB/c mice were randomly divided into Control group, EAT group and 1, 25 dihydroxy vitamin D 3[1, 25(OH) 2D 3] treatment group(VitD group; n=6/group). HE staining was used to observe thyroid pathology. Plasma thyroglobulin antibody(TGAb), thyroid peroxidase antibody(TPOAb), and 1, 25(OH) 2D 3 were measured by ELISA. Peripheral NETs formation, Th1, Th2, and Th17 cell ratio from spleen were measured by flow cytometry. Correlation between NETs formation rate and Th1, Th2, and Th17 cell ratio was analyzed. Results:Compared with Control group, mice in EAT group had significantly increased thyroid inflammation scores, thyroiditis morbidity, TPOAb, TGAb levels, NETs formation rate, Th2(CD4 + IL-4 + or CD4 + IL-13 + )and Th17 cell proportions( P were <0.001, 0.002, 0.007, <0.001, <0.001, 0.003, 0.001, and 0.002, respectively), and significant decreased 1, 25(OH) 2D 3, Th1 cell proportions, Th1/Th2(CD4 + IL-4 + ), Th1/Th2(CD4 + IL-13 + ), and Th1/Th17 ratios( P were 0.010, 0.018, 0.010, 0.005, and 0.007, respectively). Compared with the EAT group, the VitD group had lower thyroid inflammation scores, TPOAb, TGAb levels, NETs formation rate, Th2(CD4 + IL-4 + or CD4 + IL-13 + ) and Th17 cell proportions( P were 0.044, 0.007, <0.001, 0.001, 0.014, 0.008, and 0.001, respectively), and significant higher Th1 cell ratio, Th1/Th2(CD4 + IL-13 + ) and Th1/Th17 ratio( P were 0.011, 0.009, and 0.003, respectively). The Th1/Th2(CD4 + IL-4 + ) was not significantly increased in VitD group compared with EAT group( P=0.174). NETs formation rate was positively correlated with Th2(CD4 + IL-4 + or CD4 + IL-13 + ) and Th17 cell proportion( r were 0.65, 0.59, and 0.61; and P were 0.004, 0.010, and 0.007, respectively), but not with Th1 cell proportion( r=-0.47, P=0.051). Conclusion:EAT mice were more prone to NETs formation. Active vitamin D may relieve immune imbalance with increased Th2 and Th17 cell ratio and decreased Th1 cell ratio by reducing the formation of NETs in EAT mice. Vitamin D played the protective role in thyroid by reducing thyroid pathological damage and thyroid autoantibody levels, and relived overall lymphocyte imbalance.

Vitamin D and autoimmune thyroiditis in children – A prospective case–control study

Background: The deficiency or insufficiency of Vitamin D has been widely reported to be linked with autoimmune thyroid diseases. Several studies were evaluated the immunomodulatory effects of 25 hydroxyvitamin D (25(OH)D) and its counterparts in autoimmune diseases especially in autoimmune thyroiditis. Aim and Objectives: The aim of the study was to assess the Vitamin D status in children with autoimmune thyroiditis at tertiary care hospital, Sangareddy, Telangana. Materials and Methods: A source of 80 newly diagnosed cases with autoimmune thyroiditis and similar volume of age and sex matched control subjects between ?6 and 12 years were included in the study. Parameters such as thyroid function tests, serum calcium, serum phosphorus, serum alkaline phosphatase, 25(OH)D, and antithyroid antibodies levels were assessed. The antithyroid antibodies levels were assessed through chemiluminescence assay. Results: The 25(OH)D levels were 14.98ng/ml in cases and 17.46 ng/ml in control subjects. The mean levels of 25(OH)D, serum calcium, and alkaline phosphatase were statistically significant (P < 0.05). Conclusion: The levels of Vitamin D and four groups of antithyroid peroxidase antibody and antithyroglobulin antibody among cases and control subjects were not significant (P > 0.05). The estimation of Vitamin D in high-risk group may be helpful in designing the treatment strategies to decrease the morbidity.

Síndrome tirogástrico autoinmune en mujer joven

RESUMEN El síndrome tirogástrico autoinmune es la asociación entre dos patologías de origen autoinmune: la anemia perniciosa y la tiroiditis autoinmune, generalmente de presentación en adultos mayores. Se presenta caso de una mujer de 34 años que acude por derrame pericárdico asociado a una pancitopenia por déficit de vitamina B12 debida a una gastritis atrófica de origen autoinmunitaria. Se diagnostica una tiroiditis autoinmune. Recibe tratamiento con complejo B y levotiroxina, con mejoría del derrame. Es importante que ante patologías autoinmunitarias se realice la búsqueda sistemática de otras enfermedades de la misma estirpe para el mejor manejo clínico.

ABSTRACT Autoimmune thyrogastric syndrome is the association between two pathologies of autoimmune origin: pernicious anemia and autoimmune thyroiditis, which usually presents in older adults. We present the case of a 34-year-old woman who consult about pericardial effusion associated with pancytopenia caused by vitamin B12 deficiency due to autoimmune atrophic gastritis. Autoimmune thyroiditis is diagnosed. She receives treatment with complex B and levothyroxine, with improvement of the effusion. It is important that in the case of autoimmune pathologies, a systematic search for other diseases of the same lineage is carried out for the best clinical management.

Benign and malignant thyroid nodules with autoimmune thyroiditis

ABSTRACT Objective: The prevalence of autoimmune thyroiditis (AT) in papillary thyroid carcinoma (PTC) is still controversial. The aim of this study was to investigate the frequency of coexistence of PTC with AT versus that of the coexistence of benign nodules with AT. Materials and methods: This was a cross-sectional retrospective study including patients operated on for thyroid nodules from January 2011, to April 2021. The frequency of papillary carcinomas cooccurring with AT was compared to that of benign nodules cooccurring with AT, which was assessed based on cytopathological diagnosis after thyroidectomy. Results: The study included 668 cases of benign nodules and 420 cases with PTC. No statistically significant difference was observed between cases of benign and PTC nodules regarding the presence of AT (25% vs. 28%, respectively, p = 0.177). The size of the PTC compared to that of the benign predominant nodules was significantly smaller both in the absence (0.96 ± 1.09 cm vs. 2.19 ± 1.06 cm, p < 0.05) and in the presence (0.77 ± 0.76 cm vs. 1.67 ± 1.08 cm, p < 0.01) of AT. In the binary logistic regression analysis of the PTC, the only variable associated with AT was multifocality (odds ratio: 1.750, 95% confidence intervals: 1.131-2.706, p = 0.013). The incidences of lymph node involvement and advanced stage PTC were very low both in the presence and absence of AT. Conclusion: The nodules present with PTC were not more likely to coexist with AT than benign nodules were. The small incidence of advanced PTC indicates a significant improvement in early-stage diagnosis.

Structural similarity between thyroid peroxidase [Homo sapiens] and SARS-CoV-2 spike glycoprotein ­ An autoimmune thyroiditis triggering mechanism in COVID-19 carriers? / Similaridade estrutural entre a tireoperoxidase humana [Homo sapiens] e a glicoproteína de superfície do SARS-CoV-2 ­ Um mecanismo de desencadeamento da tiroidite autoimune nos portadores da COVID-19?

Introduction: there are reports of autoimmune disease related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) such neurological syndromes and hematological syndromes, and more recently autoimmune thyroid dysfunctions have been described. These reports suggest that SARS-CoV-2 acts as a probable trigger for triggering the autoimmunity process. Aim: to evaluate structural similarity between thyroid peroxidase [Homo sapiens] (TPO) and SARS-CoV-2 spike glycoprotein (COVID-19), and to propose this similarity as a likely trigger for autoimmune thyroiditis. Methodology: using bioinformatics tools, we compare the amino acids (AA) sequences between protein structure of TPO and chain A COVID-19, chain B COVID-19, and chain C COVID-19, accessible in the National Center for Biotechnology Information database, by Basic Local Alignment Search Tool in order to locate the homologous regions between the sequences of AA. Results: the homology sequence between the TPO and COVID-19 ranged from 27.0 % (10 identical residues out of 37 AA in the sequence) to 56.0% (5 identical residues out of 9 AA in the sequence). The similar alignments demonstrated relatively high E values in function of short alignment. Conclusion: data suggest a possible pathological link between TPO and COVID-19. The structural similarity of AA sequences between TPO and COVID-19 may present a molecular mimicry suggesting the possibility of antigen crossover between TPO and COVID-19 that might represent an immunological basis for autoimmune thyroiditis associated with COVID-19.

Introdução: há relatos de doenças autoimunes relacionadas à síndrome respiratória aguda grave por coronavírus 2 (SARS-CoV-2), tais como síndromes neurológicas e hematológicas, e mais recentemente disfunções autoimunes da tireoide foram descritas. Esses relatos sugerem que o SARS-CoV-2 atue como um provável gatilho para desencadear o processo de autoimunidade. Objetivo: avaliar a similaridade estrutural entre a peroxidase tireoidiana [Homo sapiens] (TPO) e a glicoproteína de superfície SARS-CoV-2 (COVID-19) e propor essa similaridade como provável gatilho para o desencadeamento da tireoidite autoimune. Metodologia: utilizando ferramentas de bioinformática, comparamos as sequências de aminoácidos (AA) entre a estrutura da TPO e a estrutura da cadeia A do COVID-19, a cadeia B do COVID-19 e a cadeia C do COVID-19, acessível no banco de dados do National Center for Biotechnology Information, através da Ferramenta Básica de Pesquisa de Alinhamento Local para localizar as regiões homólogas entre as sequências de AA. Resultados: a sequência de homologia entre o TPO e COVID-19 variou de 27,0% (10 resíduos idênticos em 37 AA nas sequências) a 56,0% (5 resíduos idênticos em 9 AA nas sequências). Os alinhamentos semelhantes demonstraram valores E relativamente altos em função do alinhamento curto. Conclusão: os dados sugerem uma possível ligação patológica entre TPO e COVID-19. A similaridade estrutural das sequências de AA entre TPO e COVID-19 pode apresentar um mimetismo molecular sugerindo a possibilidade de cruzamento de antígeno entre TPO e COVID-19 que podem representar uma base imunológica para tireoidite autoimune associada a COVID-19.

Excessive iodine promotes the occurrence and development of experimental autoimmune thyroiditis in mice through p38 and intercellular adhesion molecule-1 / 中华地方病学杂志

Objective:To investigate the molecular mechanism of excessive iodine induced experimental autoimmune thyroiditis (EAT) in mice.Methods:Sixty female non-obese diabetic (NOD) mice were selected and divided into 5 groups according to body weight [(25 ± 3) g] via the random number table method, with 12 mice in each group: control group (group A), 10-fold high iodine group (group B), 100-fold high iodine group (group C), 1 000-fold high iodine group (group D) and 1 000-fold high iodine combined with polyinosinic acid-polycytidylic acid [Poly (I:C)] group (group E). The experiment period was 16 weeks. Mice in each group drank purified water with sodium iodine (NaI) content of 0.000, 0.005, 0.050, 0.500 and 0.500 mg/L, respectively; mice in group E were intraperitoneally injected with Poly (I:C) at week 7 and week 15, respectively. At the end of the 16th week, mice were dissected and blood samples and thyroid tissue were taken. The levels of serum thyroid function indexes [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), and thyroid peroxidase antibody (TPOAb)] were detected by enzyme-linked immunosorbent assay (ELISA); the pathological changes of thyroid tissue were observed after hematoxylin-eosin (HE) staining; differentially expressed genes in thyroid tissue were detected by RNA-sequencing (RNA-seq), and analyzed by KEGG pathway; mRNA and protein levels of p38, intercellular adhesion molecule-1 (ICAM-1) and chemokine 10 (CXCL10) in thyroid tissue were detected by real-time fluorescence quantitative PCR (qPCR) and Western blotting, respectively. Results:There were statistically significant differences in serum levels of TSH (ng/ml: 6.53 ± 0.86, 6.61 ± 0.82, 7.68 ± 0.55, 7.93 ± 0.60, 8.73 ± 1.60), FT 3 (pg/ml: 59.35 ± 10.16, 53.73 ± 10.96, 46.19 ± 8.03, 41.01 ± 8.67, 34.21 ± 11.75), FT 4 (pg/ml: 136.74 ± 10.06, 124.33 ± 14.34, 101.80 ± 6.78, 91.37 ± 6.75, 73.29 ± 17.31), and TPOAb (U/ml: 130.81 ± 24.53, 145.47 ± 28.89, 166.52 ± 41.59, 199.78 ± 42.19, 201.99 ± 44.03) among the 5 groups of mice ( F = 4.77, 4.96, 23.12, 3.68, P < 0.05). Compared with group A, the serum TSH levels of mice in groups C, D and E were higher, the levels of FT 3 and FT 4 in groups B, C, D and E were lower, and the levels of TPOAb in groups D and E were higher, and the differences were statistically significant ( P < 0.05). HE staining showed that the thyroid follicle lesion in groups D and E was serious, and the EAT phenotype appeared in both groups. The differentially expressed genes were analyzed by KEGG pathway. Compared with group A, 8 metabolic pathways related to thyroid autoimmunity and inflammation were found in groups B, C, D and E. Further analysis found that 3 genes appeared in multiple pathways, namely p38, ICAM-1 and CXCL10. There were significant differences in the mRNA levels of p38, ICAM-1 and CXCL10 in thyroid tissue of the 5 groups of mice ( F = 14.77, 12.76, 16.39, P < 0.05); compared with group A, the mRNA levels of p38 in groups B, C, D and E were higher, and the mRNA levels of ICAM-1 and CXCL10 in groups C, D and E were higher ( P < 0.05). There were significant differences in the protein levels of p38, ICAM-1 and CXCL10 in thyroid tissue of the 5 groups of mice ( F = 7.97, 73.86, 18.02, P < 0.05); compared with group A, the protein levels of ICAM-1 and CXCL10 in groups B, C, D and E were higher ( P < 0.05). Conclusion:Excessive iodine promotes the occurrence and development of EAT in mice by up-regulating the expressions of p38 and ICAM-1 genes that are closely related to thyroid autoimmune and inflammatory responses.

Potential Mechanism of Buzhong Yiqitang for Autoimmune Thyroiditis Based on miRNA Sequencing / 中国实验方剂学杂志

ObjectiveTo determine the influence of Buzhong Yiqitang on miRNA expression in thyroid tissues of mice with autoimmune thyroiditis （AIT）. MethodThirty female 8-week-old NOD.H-2h4 mice were randomly assigned into normal control group， model group， and Buzhong Yiqitang group （BG）， 10 in each group. Mice were subjected to a diet containing 0.05% sodium iodide for 8 weeks to build the AIT mouse model. After 8 weeks of administration （ig）， samples were collected. A thyroid biopsy was performed on each group of mice， and differential miRNAs in thyroid tissues from each group of mice were analyzed based on experimental validation and bioinformatics. ResultCompared with the conditions of normal control group， thyroid lymphocytes had significant inflammatory infiltration， and there was an increase in serum TgAb level and interleukin（IL）-6 and IL-17 expression and a decrease in IL-1β expression in mice of the model group （P<0.05， P<0.01）. In addition， 154 differentially expressed miRNAs were found. Compared with the conditions of model group， the degree of thyroid tissue inflammation was alleviated， and serum TgAb level， and IL-1β， IL-6 and IL-17 expression of mice treated with the Buzhong Yiqitang were reduced （P<0.05， P<0.01）. Additionally， 112 differentially expressed miRNAs were identified in the BG group. Validation using real-time polymerase chain reaction（Real-time PCR） showed the same trend for miR-326-3p， miR-128-3p， miR-223-5p， miR-141-3p， miR-871-3p， and miR-204-3p as that obtained from miRNA sequencing. In particular， gene ontology（GO） functions were enriched for regulation of T cell activation， oxidative stress， and miRNA binding. Pathways identified by Kyoto encyclopedia of genes and genomes（KEGG）database tended to be enriched in phosphatidylinositol 3-kinases（PI3K）/protein kinase B（Akt）， mitogen-activated protein kinase（MAPK）， and cyclic adenosine monophosphate（cAMP） signaling pathways. Based on miRNA prediction differences， three key genes were identified： SMAD3， JAK2， and STAT3. ConclusionBushong Yiqitang might treat autoimmune thyroiditis by regulating 6 miRNAs.

Effect of Chuanshanlong Granule on TLR4/MyD88/NF-κB Signaling Pathway in Rats with Autoimmune Thyroiditis / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Chuanshanlong granule on Toll-like receptor 4 （TLR4）/myeloid differentiation protein 88 （MyD88）/nuclear transcription factor -κB （NF-κB） signaling pathway， and to explore the mechanism of its treatment of autoimmune thyroiditis （AIT） in rats. MethodForty AIT models were established following excess iodine and injection of porcine thyroglobulin and Freund's adjuvant into Lewis rats for six weeks. Then the rats were randomly divided into the model group， Chuanshanlong granule low-， medium- and high-dose group （0.52， 1.03， 2.06 g·kg-1·d-1）， with ten in each group. Rats in the Chuanshanlong granule low-， medium- and high-dose groups were separately given 0.01 mL·g-1·d-1 Chuanshanlong granule， and those in the normal group and the model group were given the same volume of deionized water for eight weeks. Serum of rats was taken to measure thyroglobulin antibody （TgAb） and thyroid peroxidase antibody （TPOAb） by enzyme-linked immunosorbent assay （ELISA）， and the concentrations of free triiodothyronine （FT3）， free thyroxine （FT4） and thyroid stimulating hormone （TSH） were detected. The rat thyroid lobes were stained with hematoxylin and eosin （HE）， and the pathological changes were observed under light microscope. In addition， the relative expression of TLR4， MyD88， NF-κB protein and mRNA was determined by immunohistochemistry and real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in the normal group， the serum concentrations of TPOAb and TgAb （P<0.01） and FT3 and FT4 （P<0.01） increased and TSH decreased （P<0.01） in the model group. Compared with the conditions in the model group， the concentrations of TPOAb and TgAb in the Chuanshanlong granule treatment groups reduced （P<0.01）， and the concentrations of FT3 and FT4 were lowered （P<0.01） while TSH increased （P<0.01） in the Chuanshanlong granule high-dose group. HE staining showed that there was lymphocyte infiltration in the thyroid follicular space， a large number of destroyed or diminished follicular cavities， decreased colloid content， and thinned or destroyed follicular wall in the model group， while the thyroid lymphocyte infiltration in the Chuanshanlong granule treatment groups was significantly less and the structure of thyroid follicles was more complete than those in the model group. Compared with the normal group， the model group had up-regulated relative expression of TLR4， MyD88 and NF-κB protein （P<0.01） and mRNA （P<0.01）. Compared with the model group， the Chuanshanlong granule high-dose group had down-regulated relative expression of TLR4 protein and mRNA （P<0.05）， MyD88 protein （P<0.01） and mRNA （P<0.05）， and NF-κB protein and mRNA （P<0.01）. ConclusionChuanshanlong granule may play a therapeutic role in AIT by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway.

Potential targets for the hepatitis C virus-mediated autoimmune thyroiditis

2021.174934ABSTRACTIntroduction: The mechanisms by which hepatitis C virus (HCV) infection induces autoimmune thyroiditis (AIT) have been studied, and it was suggested that inflammatory cytokines during HCV infection would change the thy-roperoxidase (TPO) signaling cascade and thyroglobulin (Tg) determining autoimmune thyroid disease.Objective: To show the signaling pathway, of TPO and Tg, and their potential targets mediated HCV in individuals with hepatitis C.Methods: The mapping of the signaling pathway was based on a review study approach and performed using the automatic annotation server of the Kyoto and Genome Encyclopedia (KEGG). PathVisio is free software for analysis and design of open source routes, and was used for the graphic representation of the signaling pathway.Results: The contigs were extracted from the KEGG database and their mapped transcription represents the signa-ling pathway of the main biomolecules that triggers the AIT. The action of HCV, or its treatment can trigger AIT that is characterized by the presence of autoantibodies against TPO and Tg. In AIT, autoreactive CD4 + T lymphocytes recruit B cells and CD8 + T cells in the thyroid. The progression of the disease leads to the death of thyroid cells and hypothyroidism. Conclusion: HCV or its treatment activates several signaling pathways with thyroid cells damage resulting in AIT and secondary hypothyroidism to cellular apoptosis. (AU)

RESUMOIntrodução: Os mecanismos pelos quais a infecção com o vírus da hepatite C (HCV) induz à tireoidite autoimune (TAI) têm sido alvo de estudos. Tem sido sugerido que citocinas inflamatórias, como a elevação das interleucinas na inflamação causadas pelo HCV, alterariam a cascata de sinalização da tireoperoxidase (TPO) e tireoglobulina (Tg) determinando um quadro de doença autoimune da tireóide.Objetivo: Demonstrar a via de sinalização da TPO e da Tg e seus potenciais alvos para a TAI mediados pelo HCV em indivíduos com hepatite C.Método: O mapeamento da via de sinalização foi realizado usando o servidor de anotação automática da Enciclopé-dia Quioto de Genes e Genomas (KEGG). O PathVisio, um software gratuito de análise e desenho de vias de código aberto, foi utilizado para a representação gráfica da via de sinalização.Resultado: As sequências foram retiradas do banco de dados KEGG e sua transcrição mapeada representa a via de . sinalização das principais biomoléculas que desencadeia a TAI. A ação do HCV, ou seu tratamento pode desen-cadear a TAI que é caracterizada pela presença de autoanticorpos contra a TPO e Tg. Na TAI os linfócitos T CD4+ auto-reativos recrutam células B e células T CD8+ na tireóide. A progressão da doença leva à morte de células da tireóide e hipotireoidismo.Conclusão: O HCV ou o seu tratamento ativa várias vias de sinalização com dano na célula tireoidiana, tendo como resultado TAI e hipotireoidismo secundário a apoptose celular. (AU)

Frequency of alleles associated with celiac disease in patients with autoimmune thyroid disease / Frequência dos alelos associados com a doença celíaca em portadores de doenças autoimunes da tireoide

ABSTRACT Objective To determine the frequency of Human leukocyte antigen alleles and to verify the association of the presence of these alleles with symptoms and other diseases related to celiac disease in patients with autoimmune thyroid diseases. Methods A questionnaire on the symptoms and diseases associated with celiac disease was applied. Genomic deoxyribonucleic acid was extracted by collecting cells from the oral mucosa. The alleles (DQA1*0501; DQB1*0201; DRB1*04) were identified by means of the polymerase chain reaction. Results A total of 110 patients with autoimmune thyroid diseases participated in this study. It was observed that 66.4% of the individuals carried at least one of the alleles assessed and that 58.2% of the individuals were positive for at least one of the DQ2 alleles (DQA1*0501; DQB1*0201) and out of these 18.2% were positive for both DQ2 alleles (DQA1*0501; DQB1*0201). With regard to DQ8 (DRB1*04), 21.8% of the studied population was positive for this allele and 3.6% was positive for both DQ2 (DQA1*0501; DQB1*0201) and DQ8 (DRB1*04). A significant association was found between the presence of the DRB1*04 allele and gastrointestinal symptoms (p=0.02). A significant association of the DRB1*04 allele with type 1 diabetes mellitus (p=0.02) was observed. Conclusion The genetic profiles most commonly associated with celiac disease, such as DQ2 (DQA1*0501; DQB1*0201) and DQ8 (DRB1*04) were around 20.0% prevalent in the studied population. These are risk haplotypes for celiac disease especially when symptoms and diseases related to celiac disease are present. Therefore, it is important to screen patients to investigate a potential diagnosis for celiac disease.

RESUMO Objetivo Determinar a frequência dos alelos do Human leukocyte antigen e verificar a associação da presença desses alelos com sintomas e outras doenças relacionados à doença celíaca em portadores de doenças autoimunes da tireoide. Métodos Aplicou-se um questionário relacionado aos sintomas e doenças associados à doença celíaca. O ácido desoxirribonucleico genômico foi extraído por meio da coleta das células da mucosa bucal. Os alelos (DQA1*0501; DQB1*0201; DRB1*04) foram identificados por meio da reação em cadeia da polimerase. Resultados Participaram deste estudo 110 portadores de doenças autoimunes da tireoide. Observou-se que 66,4% dos indivíduos carregavam pelo menos um dos alelos estudados e que 58,2% dos indivíduos eram positivos para pelo menos um dos alelos DQ2 (DQA1*0501; DQB1*0201) e destes 18,2% foram positivos para ambos alelos do DQ2(DQA1*0501; DQB1*0201). Com relação ao DQ8 (DRB1*04), 21,8% da população estudada eram positivos para esse alelo e 3,6% eram positivos tanto para o DQ2 (DQA1*0501; DQB1*0201) quanto para o DQ8 (DRB1*04). Foi encontrada associação significativa da presença do alelo DRB1*04 com os sintomas gastrointestinais (p=0,02). Houve associação significativa do alelo DRB1*04 com diabetes mellitus tipo 1 (p=0,02). Conclusão O perfil genético mais fortemente associado à doença celíaca, tais como DQ2 (DQA1*0501; DQB1*0201) e DQ8 (DRB1*04) estavam presentes em torno de 20,0% da população estudada, estes são haplótipos de risco para doença celíaca e principalmente na presença de sintomas e doenças relacionadas à doença celíaca. Sendo assim, é importante realizar o rastreamento para investigar um possível diagnóstico para doença celíaca.

Is there any association between vitamin D deficiency and anti-thyroid peroxidase positive hypothyroidism: A cross-sectional study

Background: Vitamin D deficiency is prevalent worldwide and it is believed to have a role as an immune modulator. However, the association between vitamin D levels and anti-thyroid peroxidase positive (TPOAb) hypothyroidism is still controversial. Aim: To elucidate the association between vitamin D levels and anti-thyroid peroxidase (TPOAb) positive hypothyroidism. Materials and Methods: Serum Vitamin D, thyroid peroxidase antibody, and thyroid function test were measured in 105 patients, who were sub-grouped into the TPOAb positive and TPOAb negative hypothyroidism category. Results: Vitamin D level, was found significantly lower in patients with TPOAb positive hypothyroidism as compared to patients TPOAb negative hypothyroidism (13.275.18vs. 17.746.03ng/ml, respectively, P<0.05), as well as between patients with TPOAb positive hypothyroidism and control group (13.275.18vs. 29.669.41 ng/ml, respectively, P<0.05). Within the patients' group, there was a significant negative correlation between serum 25 (OH) vitamin D and TSH (r=−0.438, P<0.05), anti-TPO (r=−0.275, P<0.05). Furthermore, insignificant positive correlations were recorded between serum 25 (OH) vitamin D, and each of T3, T4 (r=–0.056, 0.097, P>0.05). Conclusion: The current study observed significant low levels of 25(OH)D3 in TPOAb positive hypothyroid patients.

Relación entre tiroiditis autoinmune y lupus eritematoso sistémico / Relationship between autoinmune thyroiditis and systemic lupus erythematosus

Introducción: El lupus eritematoso sistémico es una enfermedad autoinmune que se caracteriza por la presencia de autoanticuerpos, los cuales, junto con el proceso inflamatorio, son los responsables de las manifestaciones clínicas de la enfermedad. Se puede asociar con otras afecciones como la tiroiditis autoinmune, la que, en ocasiones, precede al diagnóstico de lupus. Objetivo: Describir la relación entre tiroiditis autoinmune y lupus eritematoso sistémico. Métodos: Estudio descriptivo, correlacional y retrospectivo, realizado en la Consulta Externa del Hospital Andino de Chimborazo en el periodo comprendido entre enero de 2017 y julio de 2018. El universo estuvo constituido por la totalidad de los pacientes (137) que acudieron a consulta y que presentaron diagnóstico de lupus eritematoso sistémico. La muestra quedó conformada por los 97 pacientes que cumplieron los criterios de inclusión y exclusión definidos para la investigación. Se empleó la correlación de Pearson para establecer la relación existente entre tiroiditis autoinmune y lupus eritematoso sistémico. Resultados: El promedio de edad de los pacientes fue de 36,32 años, con predominio de edad entre 26 y 35 años. Predominó el sexo femenino (91,75 por ciento) y el tiempo de evolución fue menor de 3 años (46,40 por ciento). El 32,99 por ciento de los casos con lupus eritematoso sistémico presentaron también diagnóstico de tiroiditis autoinmune, que precedió al diagnóstico de lupus en un 90,63 por ciento de los casos. Conclusiones: Existe una relación entre tiroiditis autoinmune y lupus eritematoso sistémico. Ambas afecciones comparten mecanismos autoinmunes comunes, pero no queda totalmente esclarecido el mecanismo que las interrelaciona(AU)

Introduction: Systemic lupus erythematous is an autoimmune disease characterized by the presence of autoantibodies, in adition to the inflammatory process are responsible for the disease's clinical manifestations. It can be associated with other conditions such as autoimmune thyroiditis, this affection, sometimes, precedes the diagnosis of lupus. Objective: To describe the relationship between autoimmune thyroiditis and systemic lupus erythematous. Method: It is a descriptive, correlational and retrospective study, carried out in the outpatient clinic of the Andean hospital of Chimborazo in the period between January 2017 and July 2018. The universe was constituted by the totality of patients (137) who attended the consultation and who presented a diagnosis of systemic lupus erythematous. The sample was constituted by 97 patients who met the inclusion and exclusion criteria defined for the investigation. Pearson correlation was used to establish the relationship between autoimmune thyroiditis and systemic lupus erythematous. Results: The average age of 36.32 years with predominance of patients between 26 and 35 years of age. The female sex is predominated (91.75 percent) and the evolution time is less than three years (46.40 percent. 32.99 percent. of the cases with SLE also present a diagnosis of autoimmune thyroiditis that preceded the diagnosis of lupus in 90.63 percent. Conclusions: The relationship between autoimmune thyroiditis and systemic lupus erythematous is described; both conditions share common autoimmune mechanisms, but the mechanism which interrelate both conditions is not completely clarified(AU)

Advances in research on the effects of tolerance cells on the treatment of autoimmune thyroiditis / 解放军医学杂志

[Abstract] Tolerance is a state in which the human body is less responsive to changes in internal environmental status caused by drugs or other factors. Tolerance is a biological phenomenon, a natural consequence of the action of drugs or chemical factors. Altered organismal tolerance status often leads to the development of multiple autoimmune diseases. Autoimmune thyroiditis (AIT) is a particular type of autoimmune disease, and is exactly the result of an altered immune tolerance of the thyroid gland to a series of "redundant" antigen-antibody binding reactions that produce specific or non-specific inflammation leading to tissue destruction of the thyroid gland. In recent years, a variety of somatic cell therapies have been developed for the purpose of improving the body's tolerance, partially used in the clinical treatment of autoimmune diseases such as systemic lupus erythematosus, multiple sclerosis and Crohn's disease, etc. Such somatic cells that can regulate tolerance are called tolerogenic cells. The present paper will focus mainly on the specific autoimmune diseases such as AIT, discuss the promising therapeutic implications of tolerogenic cells for this group of diseases, and provide a summary of relevant studies. Hopefully, it will provide new research directions for the treatment of the disease.

Artritis reumatoide y enfermedad tiroidea autoinmunitaria / Rheumatoid arthritis and autoimmune thyroid disease

Resumen: ANTECEDENTES: Las enfermedades autoinmunitarias sistémicas, como la artritis reumatoide, pueden coexistir con enfermedades autoinmunitarias órgano-específicas. OBJETIVO: Describir una serie de casos de artritis reumatoide y enfermedad tiroidea autoinmunitaria (tiroiditis de Hashimoto, enfermedad de Graves). MATERIAL Y MÉTODO: Estudio retrospectivo en el que de enero a diciembre de 2017 se incluyeron pacientes con artritis reumatoide y enfermedad tiroidea autoinmunitaria. La artritis reumatoide se evaluó de acuerdo con los criterios diagnósticos de 2010 (ACR/EULAR). RESULTADOS: Se identificaron 26 pacientes con artritis reumatoide y enfermedad tiroidea autoinmunitaria. En 14 casos la manifestación inicial fue artritis reumatoide y en 12 la manifestación inicial fue enfermedad de Graves. Todos los pacientes (mujeres, mediana de edad: 46 años) acudieron con un cuadro clínico de poliartritis simétrica de las manos, los carpos y las rodillas. En total, la serología fue positiva para factor reumatoide (21), anticuerpo contra péptidos cíclicos citrulinados (11), anti-peroxidasa (21) y TSH elevada (15). En 5 casos, la enfermedad de Graves precedió a la artritis reumatoide. En cuatro casos se encontró anormalidad palpable de la glándula tiroidea. El tratamiento consistió en hormonas tiroideas sintéticas, yodo radioactivo, cirugía de tiroides y fármacos modificadores de artritis reumatoide. CONCLUSIÓN: En esta serie de casos, la causa más común de hipotiroidismo fue tiroiditis de Hashimoto que precedió o siguió el diagnóstico de artritis reumatoide.

Abstract: BACKGROUND: Systemic autoimmune diseases including rheumatoid arthritis can coexist with organ-specific autoimmune diseases. OBJECTIVE: To report a case series of rheumatoid arthritis patients who developed autoimmune thyroid disease (Hashimoto's thyroiditis, Graves' disease). MATERIAL AND METHOD: A retrospective study was done from January to December 2017 including patients with rheumatoid arthritis and autoimmune thyroid disease. Rheumatoid arthritis was assessed according to the diagnostic criteria of 2010 (ACR/ EULAR). RESULTS: There were identified 26 cases with rheumatoid arthritis and an autoimmune thyroid disease. In 14 cases rheumatoid arthritis was the initial manifestation and in 12 the initial manifestation was hypothyroidism or Graves' disease (GD). All the patients (females, median age: 46) had symmetrical polyarthritis of hands, wrists and knees. In total, serology was positive for rheumatoid factor (21), anti-cyclic citrullinated peptide antibody (11), anti-thyroid peroxidase antibody (21) and elevated levels of TSH in 15 cases. In 5 cases, hyperthyroidism was the initial feature. Palpable abnormality of the thyroid gland was present in 5 cases. The treatment consisted on synthetic thyroid hormones, radioactive iodine therapy, thyroid surgery and disease modifying drugs. CONCLUSION: In this case series, the most common cause of hypothyroidism was Hashimoto's thyroiditis preceding or following rheumatoid arthritis.

Hashimoto‘S Encephalopathy Case Reports Of Hashimoto‘S Encephalopathy In Tertiary Care Hospital

Hashimoto's encephalopathy (HE) is an uncommon syndrome and rare disease, associated with Hashimoto thyroiditis. It is characterized by a acute to chronic loss of cognitive dysfunction ,subacute onset of confusion with altered level of consciousness, stroke like episodes , neuropsychiatric manifestations ,seizures, and myoclonus. HE is believed to be an immune-mediated disorder rather than representing the direct effect of an altered thyroid state on the central nervous system. Hashimoto encephalopathy or Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) and a more general term, nonvasculitic autoimmune meningoencephalitis, are also used to describe this condition. Here we are reporting 3 cases of hashimoto encephalopathy in the tertiary care centre who presented with acute to chronic memory loss , neuropsychiatric disturbances, complex parital seizures visual hallucinations and myoclonus and responded to steroids. A negative microbiological screen of the CSF and serum along with raised CSF protein, elevated serum antithyroid antibodies, characteristic EEG and neuroimaging findings yielded the diagnosis

Increased expression of Siglec-1 on peripheral blood monocytes and its relationship with inflammatory reaction in autoimmune thyroiditis / 中华内分泌代谢杂志

Objective To investigate the expression of sialic acid-binding immunoglobulin-like-lectin-1 (Siglec-1)in the peripheral blood mononuclear cell (PBMC) of patients with autoimmune thyroiditis ( AIT) and its relationship with AIT. To explore the moduratory role of activated Siglec-1 on the differentiation of T cells and the promotion of in flammation after PBMC culture. Methods The peripheral whole blood and serum samples were collected from 30 AIT patients with normal thyroid function and 30 sex-and age-matched controls. The expression of sSiglec-1 in serum was detected by ELISA. The expression of Siglec-1 in PBMC was detected by RT-PCR and WB. The expression of Siglec-1 in CD14+ monocytes and the proportion of Th1 and Th17 cells in each group were detected by flow cytometry. The PBMC in AIT or control was stimulated with NaI in the presence or absence of LPS for 72 h. The expression of Siglec-1 in CD14+ monocytes and the proportion of Th1 and Th17 cells were detected by flow cytometry. Results sSiglec-1 in serum, Siglec-1 mRNA, and Siglec-1 protein in AIT patients'PBMC were higher than those in control group ( P＜0. 01). The expression of Siglec-1 in CD14+ monocytes by flow cytometry and differentiation of Th1 and Th17 cells were significantly higher than that in control group ( both P＜0. 01). The expression of Siglec-1 in control and AIT patients was up-regulated by 5×10-5 mmol/L to 1×10-2 mmol/L stimulated with NaI in the presence or absence of LPS for 72 h (P＜0.01), but the differentiation of Th1 and Th17 cells was up-regulated only in patients (P＜0.01), and in a dose-dependent manner. Conclusion Elevated Siglec-1 expression in PBMCs and monocytes can potentially serve as a biomarker for AIT. Iodine may affect Th1 and Th17 cell differentiation by activating Siglec-1 to adjust the AIT immune response.

Psychotic Symptoms of Hashimoto's Encephalopathy: A Diagnostic Challenge

Hashimoto's encephalopathy (HE) is a rare and underdiagnosed neuropsychiatric illness. We present the case of a 17-year-old girl who was admitted to a tertiary-care psychiatric center with acute onset psychosis and fever. Her psychotic symptoms were characterized by persecutory and referential delusions, as well as tactile and visual hallucinations. Her acute behavioral disturbance warranted admission and treatment in a psychiatric setting (risperidone tablets, 3 mg/day). She had experienced an episode of fever with a unilateral visual acuity defect approximately 3 years before admission, which was resolved with treatment. Focused clinical examination revealed an enlarged thyroid, and baseline blood investigations, including thyroid function test results were normal. Abnormal laboratory investigations revealed elevated anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels (anti-TPO of 480 IU/mL; anti-TG of 287 IU/mL). Results of other investigations for infection, including cerebrospinal fluid examination, electroencephalography, and brain magnetic resonance imaging were normal. She was diagnosed with HE and was treated with intravenous corticosteroids (methylprednisolone up to 1 g/day; tapered and discontinued after a month). The patient achieved complete remission of psychotic symptoms and normalization of the anti-thyroid antibody titers. Currently, at the seventh month of follow-up, the patient is doing well. This case highlights the fact that in the absence of well-defined clinical diagnostic criteria, a high index of suspicion is required for early diagnosis of HE. Psychiatrists need to explore for organic etiologies when dealing with acute psychiatric symptoms in a younger age group.