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.

[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.

Determination of HLA class II risk alleles and prediction of self/non-self-epitopes contributing Hashimoto's thyroiditis in a group of Iranian patients.

One of the probable hypotheses for the onset of autoimmunity is molecular mimicry. This study aimed to determine the HLA-II risk alleles for developing Hashimoto's thyroiditis (HT) in order to analyze the molecular homology between candidate pathogen-derived epitopes and potentially self-antigens (thyroid peroxidase, TPO) based on the presence of HLA risk alleles. HLA-DRB1/-DQB1 genotyping was performed in 100 HT patients and 330 ethnically matched healthy controls to determine the predisposing/protective alleles for HT disease. Then, in silico analysis was conducted to examine the sequence homology between epitopes derived from autoantigens and four potentially relevant pathogens and their binding capacities to HLA risk alleles based on peptide docking analysis. We identified HLA-DRB1*03:01, *04:02, *04:05, and *11:04 as predisposing alleles and DRB1*13:01 as a potentially predictive allele for HT disease. Also, DRB1*11:04 ~ DQB1*03:01 (Pc = 0.002; OR, 3.97) and DRB1*03:01 ~ DQB1*02:01 (Pc = 0.004; OR, 2.24) haplotypes conferred a predisposing role for HT. Based on logistic regression analysis, carrying risk alleles increased the risk of HT development 4.5 times in our population (P = 7.09E-10). Also, ROC curve analysis revealed a high predictive power of those risk alleles for discrimination of the susceptible from healthy individuals (AUC, 0.70; P = 6.6E-10). Analysis of peptide sequence homology between epitopes of TPO and epitopes derived from four candidate microorganisms revealed a homology between envelop glycoprotein D of herpes virus and sequence 151-199 of TPO with remarkable binding capacity to HLA-DRB1*03:01 allele. Our findings indicate the increased risk of developing HT in those individuals carrying HLA risk alleles which can also be related to herpes virus infection.

Changes in TgAb and TPOAb titers are greater in thyrotoxicosis than isolated hypothyroidism induced by PD-1 blockade.

Anti-thyroglobulin antibodies (TgAb) and/or anti-thyroid peroxidase antibodies (TPOAb) positivity at baseline is a risk marker for thyroid immune-related adverse events (thyroid-irAEs) in anti-programmed cell death-1 antibody (PD-1-Ab) treatment; however, it is unknown if TgAb and TPOAb titers are associated with clinical characteristics of thyroid-irAEs. Among 586 patients treated with PD-1-Ab at Nagoya University Hospital between 2 November 2015 and 30 September 2021, 57 patients developed thyroid-irAEs (thyrotoxicosis [n = 38]; hypothyroidism without prior thyrotoxicosis {isolated hypothyroidism} [n = 19]) in whom thyroid function, and TgAb and TPOAb titers were determined at baseline and at the onset. The changes in TgAb (median, 54.8 vs. 0.2 IU/mL; p = 0.002) and TPOAb titers (31.6 vs. 0 IU/mL; p = 0.032) from baseline to onset of developing thyroid-irAEs were greater in patients with thyrotoxicosis than patients with isolated hypothyroidism. Higher TgAb and TPOAb titers, and the TgAb titer at baseline were associated with an earlier onset of thyrotoxicosis and higher peak free thyroxine levels, respectively. Twenty-eight patients who developed hypothyroidism after thyrotoxicosis had higher TgAb (54.5 vs. 10.7 IU/mL; p = 0.011) and TPOAb titers at baseline (46.1 vs. 9.0 IU/mL; p < 0.001) and greater changes in TgAb (61.7 vs. 7.8 IU/mL; p = 0.025) and TPOAb titers (52.8 vs. -0.8 IU/mL; p < 0.001) than patients who did not develop hypothyroidism. The TgAb titer at baseline and changes in the TgAb and TPOAb titers were greater in patients with thyrotoxicosis than patients with isolated hypothyroidism, suggesting that the magnitude of the thyroid autoimmune response reflects the clinical types of thyroid-irAEs.

Impact of Antithyroperoxidase Antibodies (Anti-TPO) on Ovarian Reserve and Early Embryo Development in Assisted Reproductive Technology Cycles.

Autoimmune thyroid disease (AITD) is one of the most common endocrinopathies and is more prevalent in women. It becomes evident that the circulating antithyroid antibodies that often follow AITD have effects on many tissues, including ovaries, and therefore that this common morbidity might have an impact on female fertility, the investigation of which is the aim of the present research. Ovarian reserve, ovarian response to stimulation and early embryo development in infertile patients with thyroid autoimmunity were assessed in 45 women with thyroid autoimmunity and 45 age-matched control patients undergoing infertility treatment. It was demonstrated that the presence of anti-thyroid peroxidase antibodies is associated with lower serum anti-Müllerian hormone levels and antral follicle count. Further investigation revealed the higher prevalence of sub-optimal response to ovarian stimulation in TAI-positive women, lower fertilization rate and lower number of high-quality embryos in this group of patients. The cut-off value for follicular fluid anti-thyroid peroxidase antibody affecting the above-mentioned parameters was determined to be 105.0 IU/mL, highlighting the necessity of closer monitoring in couples seeking infertility treatment with ART.

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.

Value of Thyroid Peroxidase Antibodies in Neuroimmune Diseases: Analysis of Interference During Treatment with Intravenous Immunoglobulins.

OBJECTIVE: The absence of specific markers can make the diagnosis of neuroimmune disorders difficult, making other biomarkers such as thyroid peroxidase antibodies (TPO-Abs) more relevant. Laboratory tests are susceptible to interference, especially those tests performed using immunoassay techniques. The effect of treatment with human intravenous immunoglobulin (IVIG) on the results of TPO-Abs assays has not been previously characterized. MATERIALS AND METHODS: We analyzed TPO-Abs levels in 170 children monitored in the neuroimmune disease department of a tertiary hospital. We analyzed the characteristics of patients with increased TPO-Abs values and compared their progress with and without treatment. RESULTS: We found that 97% of patients with elevated TPO-Abs had received IVIG. After withdrawal from IVIG, a mean TPO-Abs decrease of 62.5% at 1 month was observed. The IVIG drug preparation was found to contain 1176 U/mL of TPO-Abs. An interferogram confirmed interference. CONCLUSION: It is advisable to measure levels of TPO-Abs before starting immunotherapy and remain vigilant regarding possible interference in the event of unsubstantiated elevations of this analyte.

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.

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.

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.

Determinants and Clinical Implications of Thyroid Peroxidase Antibodies in Middle-Aged and Elderly Individuals: The Rotterdam Study.

Background: Thyroid peroxidase antibodies (TPO-Abs) play an important role in autoimmune thyroid disease, but are also prevalent in healthy individuals. However, it is unclear what determinants may influence the occurrence of TPO-Abs in healthy individuals and how TPO-Abs may affect health outcomes in these individuals. We aimed to identify determinants of TPO-Abs in a large, prospective population-based cohort of middle-aged and elderly individuals and to subsequently assess the association between TPO-Abs and risk of overall and cause-specific mortality. Methods: We performed binomial and multinomial logistic regression analyses to obtain odds ratios (ORs) and 95% confidence intervals [95% CIs] for the association of potential determinants based on previous literature with TPO-Ab positivity (>35 kU/L), TPO-Ab detectability (>5 kU/L), and TPO-Ab categories. Cox proportional hazards regression analyses were performed to obtain hazard ratios (HRs) and CIs for the association between TPO-Abs and mortality risk. Results: In 9685 participants (57% women, median baseline age 63.3 years, median follow-up time 10.1 years), we identified female sex (OR = 2.47 [CI 2.13-2.86]) and current smoking (OR = 3.10 [CI 2.66-3.62]) as determinants of TPO-Ab positivity and TPO-Ab detectability, respectively. Higher age (OR = 0.98 [CI 0.97-0.98]) and all categories of alcohol consumption (ORs ranging from 0.71-0.78) were associated with lower odds of TPO-Ab detectability. TPO-Ab detectability was associated with a higher risk of overall (HR = 1.09 [CI 1.01-1.17]), cancer-related (HR = 1.18 [CI 1.01-1.38]), and cardiovascular mortality (HR = 1.21 [CI 1.01-1.45]). Interestingly, this was more prominent in men compared with women (HR for cardiovascular mortality 1.50 vs. 0.99, respectively). Conclusions: In community-dwelling middle-aged and elderly individuals, female sex and current smoking are the most important determinants associated with TPO-Ab levels in the detectable and positive range, whereas alcohol consumption is associated with lower odds of TPO-Abs. The clinical importance of detectable TPO-Ab levels is illustrated by the association with an increased mortality risk, mainly in men. Our results warrant further exploration of the clinical applicability of detectable TPO-Ab levels, potentially as a marker for low-grade inflammation. The Rotterdam Study has been entered into the Netherlands National Trial Register (NTR; www.trialregister.nl) and into the WHO International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/network/primary/en/) under shared catalogue number NTR6831.

Genome-wide analysis of thyroid function in Australian adolescents highlights SERPINA7 and NCOA3.

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.

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.

Relationship between autoimmune thyroid disease and nephropathy: A clinicopathological study.

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.

The impact of exogenous vitamin D on thyroid autoimmunity in euthyroid men with autoimmune thyroiditis and early-onset androgenic alopecia.

BACKGROUND: Early-onset androgenic alopecia is regarded as the phenotypic equivalent of polycystic ovary syndrome in men. Women with polycystic ovary syndrome are at high risk of autoimmune thyroiditis. The aim of the current study was to investigate whether early-onset androgenic alopecia determines the impact of exogenous vitamin D on thyroid autoimmunity and thyroid function in men with autoimmune thyroiditis. METHODS: The study included 67 young men with autoimmune thyroiditis, 25 of whom had early-onset androgenic alopecia (group A). All 25 men with alopecia and 23 out of the 42 men with no evidence of hair loss, matched for age, antibody titers and thyrotropin levels (group B), were then treated with vitamin D (100 µg daily). Serum titers of thyroid peroxidase and thyroglobulin antibodies, serum levels of thyrotropin, free thyroid hormones, total and calculated free testosterone, dehydroepiandrosterone-sulfate, estradiol, prolactin and 25-hydroxyvitamin D, as well as the calculated parameters of thyroid homeostasis were assessed before vitamin D treatment and 6 months later. RESULTS: At baseline, thyroid antibody titers were higher in subjects with than without alopecia and correlated with calculated free testosterone levels. Vitamin D reduced antibody titers in both groups but this effect was stronger in group B than group A. Only in group B, vitamin D increased SPINA-GT. The impact of vitamin D on antibody titers correlated with 25-hydroxyvitamin D levels, calculated free testosterone, treatment-induced increase in 25-hydroxyvitamin D levels and the improvement in insulin sensitivity. CONCLUSION: This study suggests that euthyroid men with early-onset androgenic alopecia may benefit to a lesser degree from vitamin D treatment than other subjects with autoimmune thyroiditis.

The association between subclinical hypothyroidism and TPOAb positivity with infertility in a population-based study: Tehran thyroid study (TTS).

BACKGROUND: Thyroid autoimmunity(TAI) is the most prevalent autoimmune condition in women of fertile age. There are increasing data regarding the association of thyroid dysfunction and thyroid autoimmunity with adverse pregnancy outcomes but there is no consensus regarding infertility and TPOAb positivity; thus we aimed to evaluate the association between thyroid TPOAb positivity and infertility in females and males in a population-based study (TTS). METHODS: Cross-sectional study of 3197 female and male participants in Tehran Thyroid Study (TTS) at the framework of the Tehran Lipid and Glucose Study (TLGS). Data included biochemical measurements and a self-administered questionnaire. RESULTS: A total of 12,823 cases in phase 4, 3719 cases (2108 female and 1611 male) were analyzed. The mean TSH of the infertile female and male was 2.52 ± 2.68 µIU/ml and 3.24 ± 10.26 µIU/ml respectively. The TPO median(IQR) of women with and without a history of infertility were 6.05 (3.30-13.96)and 6.04 (3.17-11.15);(P = 0.613), they were 5.08 (3.20-125.68) and 5.31 (3.93-125.68);(P = 0.490) in male participants, respectively. Results of crude and adjusted logistic regression analysis of the development of infertility by thyroid function and TPOAb, except for fT4 in male subjects, depicted no association between infertility and other variables in both crude and adjusted models. CONCLUSION: Based on the result, thyroid autoimmunity was not associated with infertility in both females and males.

Cordyceps sinensis-derived fungus Isaria felina ameliorates experimental autoimmune thyroiditis in mice.

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.

Serum Detection of Anti-thyroid Peroxidase and Anti-thyroglobulin Antibodies in Chinese Patients With Pemphigus Vulgaris and Pemphigus Foliaceus and Literature Review.

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.

The Influence of Reducing Diets on Changes in Thyroid Parameters in Women Suffering from Obesity and Hashimoto's Disease.

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.