Expression of thyroid antigens in the female reproductive system.

Thyroid autoimmunity (TAI) has been linked to fertility disorders and pregnancy complications, even in euthyroid women. However, the exact pathophysiological mechanism underlying this association is not fully understood. This study seeks to investigate the expression of thyroid antigens within the human female reproductive system, potentially identifying targets for thyroid antibodies. Human biopsies of endometrium and follicular granulosa cells were collected and thyroperoxidase (TPO) and thyroglobulin (TG) expression was evaluated in these tissues by immunohistochemistry. Results showed, for the first time, the expression of TG protein and confirmed the presence of thyroid TPO in human endometrium and granulosa cells. Results suggest that TPO antibodies (TPOAbs) and TG antibodies (TGAbs) could interact with TPO and TG expressed in the reproductive system in patients with positive thyroid antibodies, thereby disrupting the function of TPO and TG and generating an inflammatory response, leading to fertility disorders and pregnancy complications.

L'auto-immunité thyroïdienne (AIT) est associée à des troubles de la fertilité et à des complications de grossesse, même chez les femmes euthyroïdiennes. Cependant, le mécanisme physiopathologique sous-jacent à cette association n'est pas entièrement élucidé. Cette étude vise à examiner l'expression des antigènes thyroïdiens dans le système reproducteur féminin humain, afin d'identifier des cibles potentielles pour les anticorps antithyroïdiens. Des biopsies d'endomètre et de cellules de granulosa ont été analysées pour l'expression de la thyroperoxydase (TPO) et de la thyroglobuline (TG) par immunohistochimie. Les résultats montrent, pour la première fois, l'expression de la TG et confirment la présence de la TPO dans l'endomètre et les cellules de granulosa humaines. Ces résultats suggèrent que les anticorps anti-TPO et anti-TG pourraient interagir avec la TPO et TG exprimés au niveau du système reproducteur des patientes présentant des anticorps thyroïdiens positifs, perturbant ainsi leur fonction et entraînant une réponse inflammatoire pouvant conduire à des troubles de la fertilité et des complications de grossesse.

Brain disorders in euthyroid Hashimoto's thyroiditis patients.

Hashimoto's thyroiditis (HT) is an autoimmune disorder characterized by the destruction of thyroid follicular cells by thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), leading to hypothyroidism. Hashimoto's encephalopathy (HE) is associated with elevated levels of antithyroid antibodies. An important question is whether brain alterations precede the development of HE and are present in euthyroid patients with HT, and what pathomechanisms could be responsible for these changes. A PubMed search was conducted to identify studies addressing this issue. Numerous questionnaire studies confirmed impairments in cognitive functioning, mental and physical health, and overall well-being in euthyroid HT patients. Additionally, some imaging and mouse model studies indicate that euthyroid patients with HT likely have central nervous system alterations. Antibodies may be involved in the development of these changes. Some research suggests the role of TPOAb and TgAb, while other studies highlight the involvement of coexisting antibodies. Determining whether antibodies are assessed in serum or cerebrospinal fluid (CSF) is crucial. Antibody-specific indices (ASIs) can differentiate between antibodies passively diffusing from the serum and brain-derived antibodies, and could serve as biomarkers for brain alterations in HT patients. Much more research is needed to identify reliable biomarkers and treatments that could improve the quality of life for these patients.

Development and Validation of a Prediction Model for Thyroid Dysfunction in Patients During Immunotherapy.

OBJECTIVE: This study was designed to develop and validate a predictive model for assessing the risk of thyroid toxicity following treatment with immune checkpoint inhibitors. METHODS: A retrospective analysis was conducted on a cohort of 586 patients diagnosed with malignant tumors who received programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. The patients were randomly divided into training and validation cohorts in a 7:3 ratio. Logistic regression analyses were performed on the training set to identify risk factors of thyroid dysfunction, and a nomogram was developed based on these findings. Internal validation was performed using K-fold cross-validation on the validation set. The performance of the nomogram was assessed in terms of discrimination and calibration. Additionally, decision curve analysis was utilized to demonstrate the decision efficiency of the model. RESULTS: Our clinical prediction model consisted of 4 independent predictors of thyroid immune-related adverse events, namely baseline thyrotropin (TSH, OR = 1.427, 95%CI:1.163-1.876), baseline thyroglobulin antibody (TgAb, OR = 1.105, 95%CI:1.035-1.180), baseline thyroid peroxidase antibody (TPOAb, OR = 1.172, 95%CI:1.110-1.237), and baseline platelet count (platelet, OR = 1.004, 95%CI:1.000-1.007). The developed nomogram achieved excellent discrimination with an area under the curve of 0.863 (95%CI: 0.817-0.909) and 0.885 (95%CI: 0.827-0.944) in the training and internal validation cohorts respectively. Calibration curves exhibited a good fit, and the decision curve indicated favorable clinical benefits. CONCLUSION: The proposed nomogram serves as an effective and intuitive tool for predicting the risk of thyroid immune-related adverse events, facilitating clinicians making individualized decisions based on patient-specific information.

Thyroglobulin specific IgE and a possible link to suspected penicillin induced allergic skin manifestations - cross sectional study.

Porcine thyroglobulin was important in the discovery of alpha-Gal allergy. Here, the linkage of porcine thyroglobulin-specific IgE with IgE positivity to routinely assessed allergens and to the incoming diagnosis within a population of suspected atopic individuals is explored. IgE, IgA, total IgG and IgG subclasses to porcine thyroglobulin, IgE to bovine, human thyroglobulin and meat extract were measured with ELISA. The following correlations were observed in IgE binding to porcine and bovine thyroglobulin (r = 0.910, p = 1x10-17), porcine and human thyroglobulin (r = 0.635, p = 4x10-6), human and bovine thyroglobulin (r = 0.746, p = 6x10-9) and porcine thyroglobulin and meat extract (r = 0.482, p = 0.0009). Only one out of ten samples which showed binding to porcine thyroglobulin in ELISA tested positive with ImmunoCAP alpha-Gal, implying different epitope/s. Increased IgE binding was detected towards a more electronegative fraction of porcine thyroglobulin separated according to charge and the binding could be partially inhibited by galactose. Anti-thyroglobulin IgE was found in 29.7% of the population, in subjects who were significantly younger, p < 0.0001 and it occurred more frequently in patients referred for testing penicillin specific IgE (OR 2.48, p = 0.0059) and were negative. IgE specific to porcine, bovine and possibly human thyroglobulin may be implicated in post-infectious skin manifestation misinterpreted as penicillin allergy.

Effect and mechanism of Hashimoto thyroiditis on female infertility: A clinical trial, bioinformatics analysis, and experiments-based study.

Diagnosing Hashimoto thyroiditis (HT) relies on thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) titers. The influence of these antibodies on female infertility remains a subject of debate. This study aims to explore the effect and mechanism of HT on female infertility. First, a single-center cross-sectional study was conducted to investigate whether TgAb and TPOAb are the key factors leading to female infertility. Second, bioinformatic analysis was performed to investigate the potential target molecules and pathways. Third, in vivo experiments were performed to explore the effects of elevated TgAb levels on embryo implantation in a mouse model of autoimmune thyroiditis (AIT). Four hundred and five infertile women and 155 healthy controls were enrolled in the cross-sectional study. Results indicated that the TPOAb titer was associated with female infertility, while the TgAb titer showed no significant association. The increased levels of TgAb and TPOAb are not significantly correlated with anti-Mullerian hormone. Bioinformatic analysis indicated that the common target molecules for HT and female infertility include interleukin (IL)-6, IL-10, matrix metalloproteinase 9, and tumor necrosis factor, suggesting potential regulation through multiple signaling pathways such as HIF-1, VEGF, MAPK, and Th17 cell differentiation. A certain dose of porcine thyroglobulin can successfully establish a mouse model of AIT. In this mouse model, embryo implantation and ovarian reserve remain unaffected by elevated TgAb levels. In conclusion, the serum TPOAb titer was associated with infertility due to female factors but the TgAb titer showed no significant association. A simple increase in serum TgAb titer does not affect embryo implantation and ovarian reserve in the AIT model.

Changes in thyroid hormone concentrations over time in dogs with autoimmune thyroiditis.

OBJECTIVE: The objective of this study was to follow long-term changes in the concentration of thyroid hormones in dogs with subclinical thyroiditis. SAMPLES: Samples were obtained from 125 dogs with subclinical thyroiditis. The study population included 70 female and 55 male dogs. The mean testing interval was 3.9 years from initial testing (SD, 2.3 years; range, 1 to 9 years). METHODS: Dogs with subclinical thyroiditis were identified retrospectively using results from the Orthopedic Foundation for Animals Canine Thyroid Profile performed by the Endocrinology Section of the Michigan State University Veterinary Diagnostic Lab. Owners were invited to submit follow-up serum samples with their veterinarian along with a medical history form, including subsequent treatments. RESULTS: At the time of retesting, 30% of the dogs had progressed to hypothyroidism and/or were treated with thyroxine. Fifty percent maintained positive or equivocal thyroglobulin autoantibody (TgAA) results while remaining euthyroid. Fourteen percent of the dogs became TgAA negative and remained euthyroid. In 6% of the cases tested, proper medical histories were not available, and a final classification could not be determined. CLINICAL RELEVANCE: These results indicate that most dogs with elevated thyroglobulin autoantibodies either exhibit persistent autoimmune thyroiditis with continued risk of hypothyroidism or progress to hypothyroidism when monitored for more than 1 year. Thyroid function in dogs with subclinical thyroiditis should be monitored every 12 months or if there is change in the clinical presentation.

Determination of the levels and possible associations of alpha2-macroglobulin with autoantibodies in the serum of patients with various forms of autoimmune thyroiditis.

Antibodies to thyroid peroxidase (AB-TPO), antibodies to thyroglobulin (AB-TG), and the content of α2-macroglobulin (α2-MG) have been studied in serum samples of patients with autoimmune thyroiditis (AIT). All the patients were divided into 3 groups depending on age: 25-35, 36-50, 51-65 years. We found a significant change in the thyroid panel parameters in AIT, but without significant changes in the average concentration of α2-MG in the age groups of patients. This may be due to the accumulation and retention of complexes of defective forms of α2-MG in the circulation associated with their decreased ability to bind to receptors.

Thyroglobulin Antibodies and Tumor Epitope-Specific Cellular Immunity in Papillary Thyroid Cancer.

Papillary thyroid carcinoma (PTC) is characterized by T cell infiltration and frequently by the presence of anti-thyroglobulin antibodies (TgAbs). The role of cellular immunity and of TbAbs in this context is a matter of debate. The aim of our study was to correlate the presence of TgAbs, tumor epitope-specific T cells and the clinical outcome of PTC patients. We studied n=183 consecutive patients with a diagnosis of PTC which were treated with total thyroidectomy plus 131I ablation. During a follow-up of in mean 97 months, most of the PTC patients had no signs of tumor relapse (n=157 patients). In contrast, one patient had serum Tg levels above the detection limit and<1 ng/ml, two patients Tg serum levels≥1 ng/ml and<2 ng/ml and n=23 patients had Tg serum levels≥2 ng/ml. Morphological signs of tumor recurrence were seen in 14 patients; all of these patients had serum Tg levels≥2 ng/ml. Importantly, with the exception of one patient, all TgAb positive PTC patients (n=27) had no signs of tumor recurrence as the serum Tg levels were below the assays functional sensitivities. Tetramer analyses revealed a higher number of tumor epitope-specific CD8+T cells in TgAb positive patients compared to TgAb negative PTC patients. In summary, we show that the occurrence of TgAbs may have an impact on the clinical outcome in PTC patients. This might be due to a tumor epitope-specific cellular immunity in PTC patients.

[Molecular mimicry between human thyroid peroxidase, thyroglobulin, cosinophil peroxidase, IL-24 and microorganisms antigens]. / Mimetismo molecular entre peroxidasa tiroidea humana, tiroglobulina, peroxidasa de eosinófilos, IL-24 y antígenos de microorganismos.

OBJECTIVE: Identify molecular mimicry between TPO, eosinophil peroxidase (EPX), thyroglobulin and IL24 and microorganism antigens. METHODS: Through in silico analysis, we performed local alignments between human and microorganism antigens with PSI-BLAST. Proteins that did not present a 3D structure were modeled by homology through the Swiss Modeller server and epitope prediction was performed through Ellipro. Epitopes were located in the 3D models using PYMOL software. RESULTS: A total of 38 microorganism antigens (parasites, bacteria) had identities between 30% and 45%, being the highest with Anisakis simplex. The alignment between 2 candidate proteins from A. simplex and EPX presented significant values, with identities of 43 and 44%. In bacteria, Campylobacter jejuni presented the highest identity with thyroglobulin (35%). 220 linear and conformational epitopes of microorganism antigens were predicted. Peroxidasin-like proteins from Toxocara canis and Trichinella pseudospiralis presented 10 epitopes similar to TPO and EPX, as possible molecules triggering cross-reactivity. No virus presented identity with the human proteins studied. CONCLUSION: TPO and EPX antigens shared potential cross-reactive epitopes with bacterial and nematode proteins, suggesting that molecular mimicry could be a mechanism that explains the relationship between infections and urticaria/hypothyroidism. In vitro work is needed to demonstrate the results obtained in the in silico analysis.

OBJETIVO: Identificar mimetismo molecular entre TPO, eosinofil peroxidasa (EPX), tiroglobulina e IL24 y antígenos de microorganismos. MÉTODOS: A través de análisis in silico, realizamos los alineamientos locales entre los antígenos humanos y de microorganismos con PSI-BLAST. Las proteínas que no presentaban estructura 3D, fueron modeladas por homología a través del servidor Swiss Modeller y se realizó una predicción de epítopes a través de Ellipro. Los epítopes se localizaron en los modelos 3D utilizando el software PYMOL. RESULTADOS: Un total de 38 antígenos de microorganismos (parásitos y bacterias), tuvieron identidades entre 30 y 45%, siendo los más altos con Anisakis simplex. El alineamiento entre dos proteínas candidatas de A. simplex y EPX presentaron valores importantes, con identidades de 43 y 44%. En las bacterias, Campylobacter jejuni presentó la mayor identidad con tiroglobulina (35%). Se predijeron 220 epítopes lineales y conformacionales de antígenos de microorganismos. Las proteínas similares a la peroxidasina de Toxocara canis y Trichinella pseudospiralis presentaron diez epítopes similares a TPO y EPX, como posibles moléculas desencadenantes de una reactividad cruzada. Ningún virus presentó identidad con las proteínas humanas estudiadas. CONCLUSIÓN: Los antígenos TPO y EPX compartieron potenciales epítopes de reacción cruzada con proteínas bacterianas y nematodos, lo que sugiere que el mimetismo molecular podría ser un mecanismo que explique la relación entre infecciones y la urticaria/hipotiroidismo. Se necesitan trabajos in vitro que demuestren los resultados obtenidos en el análisis in silico.

Effect of anti-thyroid antibodies on recurrent miscarriage: A meta-analysis.

SETTING: Previous studies addressed the association between anti-thyroid antibodies and recurrent miscarriage (RM), however, the role of anti-thyroid antibodies in RM patients is debatable. OBJECTIVES: Therefore, we conducted this meta-analysis and the aim of this current study was to assess whether anti-thyroid peroxidase (anti-TPO) and/or anti-thyroglobulin (anti-TG) antibody positivity was associated with RM. DESIGN: A meta-analysis was conducted. PARTICIPANTS: Recurrent miscarriage patients. METHODS: STATA 12.0 software were applied to compute odds ratios (ORs)/relative risks (RRs) and 95% CIs regarding association between anti-TPO and anti-TG antibodies and the prevalence of RM. RESULTS: N = 28 studies (8875 participants) explored effect of anti-thyroid antibodies on RM. Analysis of the 28 studies revealed significant association between anti-TPO, anti-TG antibodies and the prevalence of RM with a random effects model (OR/RR = 2.02; 95% CI: 1.63-2.51, p < 0.001; I2 = 44.3%, p value for Q test = 0.004). Analysis of the 20 studies revealed significant association between anti-TPO antibodies and the prevalence of RM with a random effects model (OR/RR = 1.59; 95% CI: 1.25-2.03, p < 0.001; I2 = 43.1%, p value for Q test = 0.022). Analysis of the 14 studies revealed significant association between anti-TG antibodies and the prevalence of RM with a random effects model (OR/RR = 2.25; 95% CI: 1.56-3.23, p < 0.001; I2 = 49.2%, p value for Q test = 0.019). CONCLUSIONS: Based on the currently available analysis, our findings suggest that women with anti-TPO and/or anti-TG antibodies have a higher risk of RM than that in negative antibody women. Further investigation is needed to better clarify the exact role of the anti-thyroid antibodies in RM and whether treatment is of benefit. LIMITATIONS: First, differences from various detection methods and reagents used in different studies may affect the diagnostic interpretation of anti-thyroid antibodies, which might influence the accuracy of this meta-analysis. Second, positive anti-thyroid antibodies seem likely to be part of a more general disorder of maternal immune system, due to restrictions of funding and condition, a complete autoantibody screening investigation is hardly to conduct in all participants, and this could be a possible limitation of all included studies. Third, there is no mention of thyroxine therapy on RM, making the meta-analysis even more limited.

The Danish investigation on iodine intake and thyroid disease (DanThyr): history and implications.

Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild-moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program - as IF - is initiated.

Clinical use of thyroglobulin: not only thyroid cancer.

Thyroglobulin (TG) is a dimeric glycoprotein produced exclusively by mature thyroid tissue and stored within the follicular lumen. It is essential for the organification of iodine and the production of thyroid hormones. The concentration of TG in the bloodstream varies between individuals and depends on factors such as thyroid mass, stimulation of the gland by thyrotropin or autoantibodies, and tissue destruction. TG is essential to monitor patients with differentiated thyroid cancer; however, its use is not limited only to this clinical entity. Measurement of circulating TG can provide better insight into numerous clinical scenarios, such as destructive thyroiditis, presence of ectopic thyroid tissue, thyroid trauma, factitious thyrotoxicosis, or iodine nutrition. Lately, TG has found its new clinical use in immune checkpoint-related thyroid dysfunction. TG measurement should be performed carefully in patients with antithyroglobulin antibodies due to possible laboratory interferences. In this review, we offer a summary of current knowledge about the clinical use of TG and the implications it brings to daily practice.

Sex-Specific Effect of Thyroid Peroxidase Antibody and Thyroglobulin Antibody Exposure During Pregnancy on Preschoolers' Emotional and Behavioral Development: A Birth Cohort Study.

Background: Epidemiological and experimental studies suggest that thyroid peroxidase antibody (TPOAb)- and thyroglobulin antibody (TGAb)-positive exposure during gestation may contribute to offspring's adverse neural development. However, limited knowledge is available on the association between joint exposure on TPOAb and TGAb and children's emotional and behavioral development. Furthermore, the sex-specific effect on the developmental process of preschoolers' emotions and behaviors is unknown. The present research intends to examine the sex-specific effect of TPOAb- and TGAb-positive exposure in gestation on the developmental process of preschoolers' emotions and behaviors. Methods: A total of 2455 mother-child pairs were included from the Ma'anshan Birth Cohort study. The serum TPOAb and TGAb of pregnant women was measured retrospectively by electrochemical immunoassay during the follow-up period. Preschoolers' emotional and behavioral development was assessed by a child behavior checklist 1.5-5. Growth mixture modeling was adopted to fit thyroid antibody (TAb) trajectories. Poisson regression models were used, stratifying by sex, to examine the association between TAb trajectories, as well as four categories of maternal TAb exposure and preschoolers' emotional and behavioral problems. Results: Boys born to mothers with TPOAb positivity in the first, second, and third trimesters of pregnancy had an increased risk of autism spectrum problems after adjusting for confounders, with relative risk (RR) [confidence interval, CI] of 2.01 [1.24-3.27], 2.15 [1.08-4.26], and 2.13 [1.20-3.79], respectively. Maternal TGAb positivity and TPOAb negativity in the first trimester were associated with a high risk of attention-deficit/hyperactivity problems in boys (RR = 1.74 [CI 1.01-2.99]). The prevalence of depressive problems in girls was 33.3% after exposure to TPOAb alone in the third trimester of pregnancy. Exposure to TPOAb alone in the third trimester of pregnancy was associated with an increased risk of depressive problems in girls (RR = 1.78 [CI 1.09-2.90]). Conclusions: Maternal TPOAb positivity in all three trimesters was associated with the risk of autism spectrum problems in boys. Isolated maternal TGAb positivity in the first trimester was associated with attention-deficit/hyperactivity problems in boys, whereas isolated maternal TPOAb positivity in the third trimester was associated with depressive problems in girls.

Elevated Thyroid Autoantibodies Aggravate Stroke Severity in Euthyroidism with Acute Ischemic Stroke.

Introduction: Studies have indicated that immune reactions contribute to endothelial dysfunction and atherosclerosis. It is unclear whether thyroid dysfunction or elevated thyroid autoantibodies are associated with atherosclerosis. Therefore, we investigated the influence of thyroid autoimmunity related to elevated thyroid autoantibodies on functional outcome in euthyroidism with acute ischemic stroke (AIS). Methods: All patients with AIS underwent tests for thyroid function and thyroid antibodies (thyroid peroxidase antibody and thyroglobulin autoantibody). We divided the patients suffering from euthyroidism and AIS into positive thyroid autoantibody and negative thyroid autoantibody groups. Demographic profiles, risk factors, and functional outcomes were compared between the two groups. Results: Out of the total 422 patients, 50 (11.8%) were included in the positive thyroid autoantibody group. The National Institutes of Health Stroke Scale (NIHSS) score at admission and discharge was higher in the positive thyroid autoantibody group than the negative thyroid autoantibody group (P < 0.05). In addition, there was significant difference in the mortality during hospitalizations between the two groups (P < 0.01). Conclusion: This study showed that thyroid autoantibodies aggravate stroke severity in euthyroidism with AIS. We speculate that vascular damage related to thyroid autoimmunity may aggravate the increased risk of unfavorable outcomes, independent of thyroid function.

The Frequency of Intrathyroidal Follicular Helper T Cells Varies with the Progression of Graves' Disease and Hashimoto's Thyroiditis.

OBJECTIVE: Autoimmune thyroid diseases (AITD), mainly Graves' disease (GD) and Hashimoto's thyroiditis (HT), are common organ-specific autoimmune diseases characterized by circulating antibodies and lymphocyte infiltration. Follicular helper T (Tfh) cell dysregulation is involved in the development of autoimmune pathologies. We aimed to explore the role of intrathyroidal and circulating Tfh cells in patients with GD and HT. METHODS: Ultrasound-guided thyroid fine-needle aspiration (FNA) was conducted in 35 patients with GD, 40 patients with HT, and 22 patients with nonautoimmune thyroid disease (nAITD). Peripheral blood samples were also obtained from 40 patients with GD, 40 patients with HT, and 40 healthy controls. The frequencies of intrathyroidal and circulating Tfh cells from FNA and peripheral blood samples were assessed by flow cytometry. Additionally, the correlations between the frequencies of the Tfh cells and the levels of autoantibodies and hormones or disease duration were analyzed. RESULTS: The frequency of intrathyroidal CD4+CXCR5+ICOShigh Tfh cells was higher in HT patients than in GD patients. Significant correlations were identified between the percentages of circulating and intrathyroidal Tfh cells and the serum concentrations of thyroid autoantibodies, especially thyroglobulin antibodies (TgAb), in AITD. Intrathyroidal CD4+CXCR5+ICOShigh Tfh cells were positively correlated with free triiodothyronine (FT3) in HT patients but negatively correlated with FT3 in GD patients. In addition, HT patients with a longer disease duration had an increased frequency of intrathyroidal CD4+CXCR5+ICOShigh and CD4+CXCR5+PD-1+ Tfh cells. In contrast, in the GD patients, a longer disease duration did not affect the frequency of intrathyroidal CD4+CXCR5+ICOShigh but was associated with a lower frequency of CD4+CXCR5+PD-1+ Tfh cells. CONCLUSIONS: Our data suggest that intrathyroidal Tfh cells might play a role in the pathogenesis of AITD and they are potential immunobiomarkers for AITD.

Prunella vulgaris can improve the pregnancy outcomes of experimental autoimmune thyroiditis rats by inhibiting Th1/Th17 immune responses.

Autoimmune thyroiditis (AIT), one of the most common autoimmune diseases among women of reproductive age, is closely associated with reproductive failure and other obstetric complications. However, effective clinical strategies for the management of pregnant women with AIT are limited. It has been shown that Prunella vulgaris (PV), a traditional herbal medicine, can ameliorate AIT and other common thyroid disorders. Therefore, using an experimental autoimmune thyroiditis (EAT) rat model, we investigated the potential effects of PV on AIT-related pregnancy outcomes. According to the administered dose of PV, EAT rats were randomly divided into the untreated EAT and PV-treated EAT groups. We found that thyroid peroxidase antibody and thyroglobulin antibody serum levels and the inflammatory infiltration of the thyroid were reduced in all PV-treated groups. Increased splenic Tgfb1 mRNA levels and Treg cell proportions were associated with decreased Th1/Th17 cell proportions, and Ifng mRNA levels were reduced in rats that received low and medium doses of PV. Moreover, in the low-dose PV group, fetal development retardation and placental injuries were reversed. Overall, our findings indicated that PV could alleviate AIT and improve pregnancy outcomes in EAT rats by downregulating Th1/Th17 immune responses and inducing Treg cell proliferation.

Serum Antithyroglobulin Antibody Levels Are Associated with Diabetic Retinopathy among Euthyroid Type 2 Diabetes Patients: A Hospital-Based, Retrospective Study.

BACKGROUND: Previous studies have revealed that the variation of thyroid indicators may be associated with the risk of diabetic retinopathy (DR) among euthyroid type 2 diabetes (T2D) patients. But the specific conclusions are currently inconsistent. METHODS: This is a hospital-based retrospective survey. We recruited 1,145 euthyroid T2D patients and checked the thyroid function and fundus photographs. The modified Airlie House classification system was used to categorize the stages of DR. The association between thyroid indicators and different stages of DR was analyzed. RESULTS: We divided free triiodothyronine (FT3) into tertiles and found that the prevalence of mild nonproliferative DR (NPDR) was significantly higher in T2, compared with T1 (32.0% vs. 25.2%, p < 0.05). When FT3 was within the level of T2, FT3 could be an independent risk factor for mild NPDR (OR 1.426, 95% CI (1.031, 1.971), p < 0.05). In addition, the prevalence of severe NPDR and proliferative DR (PDR) was significantly higher in thyroglobulin antibody (TgAb) positive group (8.8% vs. 4.1%, p < 0.05) and vice versa (33.3% vs. 18.4%, p < 0.05). TgAb positivity was also an independent risk factor for severe NPDR and PDR (OR 2.212, 95% CI (1.244, 3.934), p < 0.05). CONCLUSIONS: We hardly observed a significant change in DR risk with the elevation or reduction of serum TSH or thyroid hormone within the reference interval. Although the slightly elevated FT3 may be associated to mild NPDR, the extensibility of this result remains to be seen. For T2D patients with euthyroid function, there may be a significant correlation between serum TgAb positivity and severe NPDR and PDR.

The expression of anti-protein disulfide isomerase A3 autoantibody is associated with the increased risk of miscarriage in euthyroid women with thyroid autoimmunity.

Miscarriage frequently occurs in euthyroid women with thyroid autoimmunity (TAI), but its mechanisms remain unclear. Our previous study has found that the serum level of anti-protein disulfide isomerase A3 autoantibody (PDIA3Ab) was significantly increased in mice with TAI. This study was aimed to explore whether there could be an association between the expression of PDIA3Ab and the occurrence of miscarriage in euthyroid TAI women. It was found that the serum level of PDIA3Ab was significantly increased in euthyroid TAI women as compared with that of non-TAI controls. Especially, serum PDIA3Ab level was markedly higher in euthyroid TAI women with miscarriage than the ones without miscarriage. Furthermore, binary logistic regression analysis showed that the serum PDIA3Ab level was an independent risk factor for spontaneous abortion in euthyroid TAI women with an odds ratio of 13.457 (95% CI, 2.965-61.078). The receiver operating characteristic (ROC) analysis of serum PDIA3Ab expression for predicting the miscarriage in euthyroid TAI women showed that the area under the curve was 0.707 ± 0.05 (P < 0.001). The optimal cut-off OD450 value of serum PDIA3Ab was 0.7129 with a sensitivity of 52.5% and specificity of 86.3% in euthyroid TAI women. Trend test showed that the prevalence of spontaneous abortion was markedly increased with the rise of serum PDIA3Ab level among TAI women in a titer-dependent manner. In conclusion, serum PDIA3Ab expression may imply an increased risk of spontaneous abortion in euthyroid TAI women, and it can be used as a new predictive bio-marker.

Presence of Anti-Thyroid Antibodies Correlate to Worse Outcome of Anti-NMDAR Encephalitis.

Objective: To investigate the characteristics and prognosis of anti-NMDAR encephalitis with the prevalence of anti-thyroid antibodies (ATAbs). Methods: The clinical data of anti-NMDAR encephalitis patients admitted to Xuanwu Hospital from January 2012 to August 2018 was prospectively analyzed, and the patients were followed up for 24 months. Results: A total of 120 patients were enrolled, of which 34.2% (41/120) were positive for ATAbs. The antibodies were more frequent in patients with severe disease compared to the non-severe group (51.4% vs. 25.6%, P=0.008). In addition, prevalence of ATAbs correlated with a higher incidence of disturbed consciousness, autonomic dysfunction, central hypoventilation and mechanical ventilation. The ATAbs-positive patients were also more likely to receive intravenous gamma immunoglobulin and immunosuppressor compared to the ATAbs-negative cases (P=0.006; P=0.035). Although the presence of ATAbs was associated with longer hospital stays and worse prognosis at 6 months (P=0.006; P=0.038), it had no impact on long-term patient prognosis. Positive status of anti-thyroglobulin antibody was an independent risk factor for worse prognosis at 6 months [odds ratio (OR)= 3.907, 95% CI: 1.178-12.958, P=0.026]. Conclusion: ATAbs are prevalent in patients with anti-NMDAR encephalitis, especially in severe cases, and correlate with poor prognosis and impaired short-term neurological recovery.

The effects of selenium supplementation on antibody titres in patients with Hashimoto's thyroiditis.

INTRODUCTION: The objective of this study was to evaluate the effect of selenium supplementation on autoantibody titres, thyroid ultrasonography, and thyroid function in patients with Hashimoto's thyroiditis (autoimmune thyroiditis) and normal thyroid reference range. MATERIAL AND METHODS: A total of 100 patients were given 200 ug/d selenium yeast orally, their thyroid function, levels of serum selenium, thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and urine iodine were measured, and thyroid ultrasonography was performed before administration and three and six months afterwards, and the data were statistically analysed. RESULTS: The subjects exhibited a selenium deficiency before the administration of selenium, and the serum levels increased to moderate levels three and six months after the selenium supplementation (p < 0.05). The titres of TGAb decreased significantly in patients after six months of selenium supplementation (p < 0.05). In the high antibody group, TgAb decreased after 6 months compared with baseline (p = p < 0.05), and TPOAb decreased after 3 and 6 months of selenium supplementation compared with baseline (p < 0.05). CONCLUSION: In patients with autoimmune thyroiditis and normal thyroid reference range, there was a general selenium deficiency, but after six months of treatment it was shown that selenium supplementation may be effective in reducing the titres of TGAb and TPOAb.