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Anxiety disorder, depression, and bipolar disorder are common psychiatric disorders, and their association with autoimmune thyroiditis (AIT) has been of great interest. This study aimed to investigate the potential causal relationship between these psychiatric disorders and AIT. We used publicly available summary statistics from large-scale genome-wide association studies to select, quality control and cluster genetic variant loci associated with anxiety disorder, depression, bipolar disorder and AIT as instrumental variables (IVs). The Mendelian randomization (MR) study mainly used inverse variance weighting (IVW) combined with MR-egger regression and weighted median estimation (WME) to estimate bidirectional causality between mental disorders and AIT. In addition, we conducted heterogeneity and multivariate tests to verify the validity of IVW. Two-sample bidirectional MR analysis revealed a positive causal link between depression and AIT. The forward MR analysis of IVW (OR 1.614, 95 % CI 1.104–2.358, P = 0.013) and WME (OR 2.314, 95 % CI 1.315–4.074, P = 0.004) demonstrated thatdepression potentially elevate the risk of AIT development, while, our investigation did not uncover a causal relationship between anxiety disorder, bipolar disorder and AIT. The results of reverse MR analysis showed that there was no significant causal relationship between AIT and anxiety disorder, depression, and bipolar disorder (P > 0.05). The results of the forward MR analysis suggest a positive association between depression, and AIT risk, while indicating no support for a causal link between anxiety disorder or bipolar disorder and AIT risk based on the current data. Subsequent studies will be essential for elucidating the biological mechanisms and potential confounders underlying these associations. • There is a causal relationship between depression and autoimmune thyroiditis (AIT). • Reverse MR analysis did not identify a causal relationship between AIT and common psychiatric disorders. • Psychiatric disorders induce AIT mainly by affecting the levels of T and B lymphocytes and by influencing the HPT axis. [ABSTRACT FROM AUTHOR]

This study aimed to identify differentially methylated genes (DMGs) associated with natural killer cells in patients with autoimmune thyroiditis (AIT), focusing on the influence of varying water iodine exposure levels. Participants were divided into categories based on median water iodine (MWI) concentrations: iodine-fortified areas (IFA, MWI < 10 μg/L), iodine-adequate areas (IAA, 40 ≤ MWI ≤ 100 μg/L), and iodine-excessive areas (IEA, MWI > 300 μg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89, 40, and 47 pairs for IFA, IAA, and IEA, respectively. DMGs were identified using 850K BeadChip analysis for 10/10 paired samples. Validation of DNA methylation and mRNA expression levels of the DMGs was conducted using MethylTarget™ and QRT-PCR for 176/176 paired samples. KLRC1 , KLRC3 , and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed, whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore, KLRC1 was hypomethylated and highly expressed in both IFA and IEA. The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally, DNA methylation of KLRC1 seems to be influenced by different iodine concentrations in water. [ABSTRACT FROM AUTHOR]

Studies have been conducted on the relationship between depression and thyroid diseases and function, its causal relationship remains unclear. Using summary statistics of genome-wide association studies of European and East Asian ancestry, we conducted 2-sample bidirectional Mendelian randomization to estimate the association between MDD and thyroid function (European: normal range TSH, T4, T3, fT4, TPOAb levels and TPOAb-positives; East Asian: T4) and thyroid diseases (hypothyroidism, hyperthyroidism, and Hashimoto's thyroiditis), and used Mediation analysis to evaluate potential mediators (alcohol intake, antidepressant) of the association and calculate the mediated proportions. It was observed a significant causal association between MDD on hypothyroidism (P = 8.94 × 10−5), hyperthyroidism (P = 8.68 × 10−3), and hashimoto's thyroiditis (P = 3.97 × 10−5) among European ancestry, which was mediated by Alcohol intake (alcohol intake versus 10 years previously for hypothyroidism (P = 0.026), hashimoto's thyroiditis (P = 0.042), and alcohol intake frequency for hypothyroidism (P = 0.015)) and antidepressant (for hypothyroidism (P = 0.008), hashimoto's thyroiditis (P = 0.010)), but not among East Asian ancestry (P MDD-hypothyroidism = 0.016, but β direction was different; P MDD-hyperthyroidism = 0.438; P MDD-hashimoto ' s thyroiditis = 0.496). There was no evidence for bidirectional causal association between thyroid function mentioned above and MDD among both ancestry (all P > 0.05). We importantly observed a significant causal association between MDD on risk of hypothyroidism, hyperthyroidism, and hashimoto's thyroiditis among European ancestry, and Alcohol intake and antidepressant as mediators for prevention of hypothyroidism, hashimoto's thyroiditis attributable to MDD. • We conducted 2-sample bidirectional Mendelian randomization to estimate the association between MDD and thyroid diseases among European and East Asian ancestry and Mediation analysis to evaluate potential mediators (alcohol intake and antidepressant). • It was observed a significant causal association between MDD on hypothyroidism, hyperthyroidism, and hashimoto's thyroiditis among European ancestry, in which MDD on hypothyroidism and hashimoto's thyroiditiswas were mediated by Alcohol intake and antidepressant, but not among East Asian ancestry. • These findings may lead to a shift in personalizing treatment in the future. [ABSTRACT FROM AUTHOR]

La sclérodermie systémique (ScS) est une maladie auto-immune rare touchant principalement la femme entre 40 et 60 ans. Elle se caractérise par une fibrose cutanée et viscérale, une altération du réseau microvasculaire et la présence d'auto-anticorps. La ScS peut être associée à une autre connectivite ou à d'autres maladies auto-immunes définissant ainsi le syndrome de chevauchement. L'objectif de notre étude est de décrire ces syndromes de chevauchement. Nous avons analysé les données d'une cohorte rétrospective et bicentrique (unité de médecine interne de l'hôpital Nord de Marseille et unité de médecine interne de l'hôpital d'instruction des Armées Sainte-Anne à Toulon) de patients suivis pour une ScS entre le 1er janvier 2019 et le 1er décembre 2021. Nous avons recueilli leurs caractéristiques cliniques, immunologiques, les maladies auto-immunes et inflammatoires associées ainsi que la morbi-mortalité. La cohorte incluait 151 patients dont 134 étaient des ScS cutanées limitées. Cinquante-deux (34,4 %) patients présentaient au moins une atteinte auto-immune ou inflammatoire associée. L'association de deux connectivites dont la ScS concernait 24 patients (15,9 %) avec un tiers de syndrome de Sjögren et un tiers de myosite auto-immune. La principale maladie auto-immune associée à la ScS était la thyroïdite auto-immune, retrouvée chez 17 patients (11,3 %). La survenue de complications (recours à l'hospitalisation, oxygénothérapie au long cours, décès) n'était pas significativement différente en fonction de l'existence d'un syndrome de chevauchement ou non. La ScS s'accompagne souvent d'autres pathologies auto-immunes. Cette intrication de pathologies associées, modifiant parfois l'évolution de la ScS, impose un suivi personnalisé. Systemic sclerosis (SSc) is a rare auto-immune disease, affecting principally women between 40 and 60 years old. It is caracterised by a cutaneous and visceral fibrosis, an alteration of the microvascular network and the presence of autoantibodies. SSc can be associated with another connectivite tissue disease or to other autoimmune diseases, thus defining the overlap syndrome. The goal of our study is to describe these overlap syndromes. We have analysed the data of a retrospective and bicentrique cohort, from the internal medicine unit of Hôpital Nord in Marseille and from the internal medicine unit of the Hôpital Sainte-Anne in Toulon, of patients followed for a SSc between January 1st, 2019 and December 1st, 2021. We have collected clinical, imunological features, associated auto-immune and inflammatory diseases with its morbidity and mortality. The cohort included 151 patients including 134 limited cutaneous SSc. Fifty-two (34.4%) patients presented at least one associated auto-immune or inflammatory disease. The association of two connectivite tissue diseases including SSc was found in 24 patients (15.9%), a third with Sjögren's syndrome and a third with autoimmune myositis. The principal associated disease to SSc was the autoimmune thyroiditis found in 17 patients (11.3%). The occurrence of complications (hospitalization, long-term oxygene therapy, death) was not significantly different depending on the existence or not of an overlap syndrom. SSc is often associated with other autoimmune diseases. This interrelation between associated pathologies and SSc, modifying sometimes the evolution of SSc, enhances the need of a personalized follow-up. [ABSTRACT FROM AUTHOR]

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common human thyroid autoimmune diseases with opposite clinical manifestations. GD and HT originate from T cells that are autoreactive to thyroid-stimulating hormone (TSH) receptor antigens and to thyroglobulin (Tg)/thyroid peroxidase (TPO) antigens, respectively. The two diseases exhibit shared risk factors and incidence curves, and can interconvert. The autoimmune surveillance theory provides a rationale for a putative shared etiology between the two diseases based on a physiological circuit of a mutant removal mechanism. Autoreactive T cells are suggested to weed out hypersecreting mutants in the thyroid, with the cost of triggering a humoral response, leading to GD or HT in susceptible individuals. The origin of the two autoimmune diseases of the thyroid (Graves' disease and Hashimoto's thyroiditis) remains insufficiently understood. Despite their opposite clinical manifestations of hyper- and hypothyroidism, we propose a shared origin based on a physiological autoimmune surveillance mechanism against hypersecreting mutant cells, which may explain observed links between these diseases. Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune diseases of the thyroid gland, causing hyperthyroidism and hypothyroidism, respectively. Despite their opposing clinical manifestation, they have several enigmatic links. Here, we propose that GD and HT have the same fundamental origin: both diseases are the cost of a beneficial physiological process called autoimmune surveillance of hypersecreting mutants. Autoreactive T cells selectively eliminate mutant cells that hypersecrete the hormones and threaten to become toxic nodules. These T cells can trigger a humoral response in susceptible individuals, leading to the production of antibodies against thyroid antigens. This shared origin can explain similarities in incidence and risk factors between HT and GD, despite their opposite clinical phenotypes. [ABSTRACT FROM AUTHOR]

The aim of the study was to focus on children with both chronic spontaneous urticaria (CSU) and autoimmune thyroiditis (AT) as this topic is rarely studied in children although some publications show a higher proportion of antithyroid antibodies in children with CSU. We highlight two cases of children with both CSU and AT and compare their data with reports from the literature. Since only case reports or case series were available, we performed a descriptive analysis of 15 patients. There were 7 (46.7%) cases of hypothyroidism and the rest were euthyroid. Hypothyroidism appears before, during, and after the diagnostic of CSU. One patient with hypothyroidism and one with euthyroidism receiving l -thyroxine experienced remission of urticaria. Three patients over 12 years of age (20%) received omalizumab. Three patients (20%) had another autoimmune disease and seven (58.3%) had a family history of thyroid disease or autoimmune disease. Children with CSU need repeated testing for antithyroid antibodies. Children with both CSU and AT require close medical supervision focused on the development of other autoimmune diseases. l -thyroxine may improve urticaria in patients with hypothyroidism, but there is not enough evidence for patients with euthyroidism. Omalizumab may be of benefit in this population but well-controlled studies in children with AT and CSU are needed. [ABSTRACT FROM AUTHOR]

We aimed to evaluate catch-up growth in children with severe Hashimoto's hypothyroidism (HH) after thyroid hormone replacement therapy (HRT). A multicenter retrospective study was conducted including children referred for growth slowdown that led to the diagnosis of HH between 1998 and 2017. A total of 29 patients were included, with a median age of 9.7 years (13–172 months). Median height at diagnosis was -2.7 [-4.6; -0.1] standard deviation score (SDS), with a height loss of 2.5 [0.7; 5.4] SDS compared to height before growth deflection (p <0.0001). At diagnosis, the median TSH level was 819.5 mIU/L [100; 1844], the median FT4 level was 0 pmol/L [undetectable; 5.4], and the median anti-thyroperoxidase antibody level was 1601 UI/L [47; 25,500]. In the 20 patients treated only with HRT, there were significant differences between height at diagnosis and height at 1 year (n = 19, p <0.0001), 2 years (n = 13, p = 0.0005), 3 years (n = 9, p = 0.0039), 4 years (n = 10, p = 0.0078), and 5 years (n = 10, p = 0.0018) of treatment but not in the case of final height (n = 6, p = 0.0625). Median final height was -1.4 [-2.7; 1,5] SDS (n = 6), with a significant difference between height loss at diagnosis and total catch-up growth (p = 0.003). The other nine patients were also given growth hormone (GH). They were smaller at diagnosis (p = 0.01); however, there was no difference in final height between those two groups (p = 0.68). Severe HH can lead to a major height deficit, and catch-up growth seems to be insufficient after treatment with HRT alone. In the most severe cases, administration of GH may enhance this catch-up. [ABSTRACT FROM AUTHOR]

There is approximately 10%–50% of papillary thyroid carcinoma (PTC) patients with Hashimoto's thyroiditis (HT). In this research, we sought to better understand the role of HT in PTC progression as well as lymph node metastasis. It is a retrospective and cross-sectional study, and 4131 PTC patients who underwent thyroidectomy were finally enrolled. Chi-square test, univariate and multivariate logistic regression analyses were employed to evaluate both the risk factors and the critical roles of HT during PTC metastasis. In this cohort, 1555 patients (37.6%) were diagnosed with HT. According to multivariate analysis, male sex, high levels of TG and TPOAb, tumor extrathyroidal extension, maximum diameter >1 cm, and multifocality were independent risk factors for both central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). In addition, age <55 years and smoking were risk factors for CLNM, while CLNM was one of the risk factors for LLNM. Furthermore, HT was suggested a valuable protective factor for both CLNM and LLNM. In patients with HT, the total number of central lymph nodes was higher, while the positive rate was lower. Compared with those without HT, age and sex did not predict CLNM and LLNM in patients with HT. HT is considered a protective factor for both CLNM and LLNM in PTC. For patients with HT, surgeons should pay more attention to the preservation of parathyroid gland and the protection of recurrent laryngeal nerve due to less lymph node metastasis. Otherwise, radical operation is highly recommended. [ABSTRACT FROM AUTHOR]

Thyroid autoimmunity is a potentially critical factor that is often neglected in the association between subclinical hypothyroidism (SCH) and depressive disorders. This study aimed to investigate the clinical correlates of autoimmune thyroiditis (AIT) and non-autoimmune hypothyroidism (NAIH) in treatment-naïve patients with major depressive disorder (MDD). Using a cross-sectional design, we recruited a total of 1718 outpatients with treatment-naïve MDD. Demographic and relevant clinical information including duration of MDD, severity of depression and anxiety, psychotic symptoms, suicide attempts, thyroid function parameters, etc. were collected. According to thyroid function parameters, patients were classified as AIT, NAIH, latent Hashimoto's thyroiditis (LH) and euthyroidism (ET). Patients with SCH (including AIT and NAIH) had older age at onset, and were more likely to have psychotic symptoms compared to those with ET. Multiple linear regression analysis showed that SCH was associated with duration of MDD and HAMD scores. Logistic regression analysis showed that the odds of having more severe anxiety and metabolic syndrome were greater among patients with SCH compared to those with ET. The odds of having suicide attempts were greater among patients with AIT than among those with ET. Because of the cross-sectional design of this study, we were unable to sort out causality between MDD and SCH. Our findings suggested that AIT and NAIH were associated with duration of MDD, HAMD scores, severity of anxiety, and metabolic syndrome. However, only AIT in SCH was associated with suicide attempts. • SCH (including AIT and NAIH) is associated with duration of MDD, HAMD scores, severity of anxiety, and metabolic syndrome. • Only autoimmune thyroiditis in subclinical hypothyroidism is associated with suicide attempts. • No significant difference between latent Hashimoto's thyroiditis and euthyroidism on all clinical characteristics. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis and Graves' disease are autoimmune diseases of the thyroid gland, and both diseases are diagnosed with ultrasound findings and autoantibody height. However, ultrasound (US) findings may be normal in both diseases rarely. In some pediatric studies, it was reported that shear wave velocity values in autoimmune thyroiditis were significantly higher than normal thyroid parenchyma and it was recommended to be used as a diagnostic method. Our study will address the evaluation of patients with Hashimoto's thyroiditis and Graves' disease by thyroid elastography and the role of this method in diagnosis. 28 patients with Hashimoto's thyroiditis, 20 patients with Graves' disease and 40 healthy controls were enrolled in our study prospectively. Thyroid Elastography and US were applied to all patients. In US, Hashimoto's thyroiditis had a hypoechoic echo pattern compared to graves' disease (p < 0.05). When shear wave velocity (SWV) value of children with Hashimoto's thyroiditis and Graves' disease were compared with the control group, thyroid tissue showed more stiffness in both disease groups (p = 0.001). When SWV values were compared between Hashimoto's thyroiditis and Graves' disease, there was no statistically significant difference (p = 0.73). SWV values were found to be higher in children with Hashimoto's thyroiditis and Graves' disease compared to the control group and contributes to the diagnosis of these diseases. However, the elastography technique alone is not sufficient to differentiate. Hashimoto's thyroiditis and Graves' disease. [ABSTRACT FROM AUTHOR]

• Serum IL-36γ level was significantly elevated in HT patients. • Serum IL-36γ level was correlated with TPO-Ab titers in HT patients. • IL-36γ may serve as a potential diagnostic biomarker for HT. Hashimoto's thyroiditis (HT) is the predominant cause of primary hypothyroidism. Interleukin (IL)-36γ is a member of the IL-36 family. Recently, IL-36γ was shown to possess proinflammatory properties in autoimmune diseases. However, the role of IL-36γ in HT is insufficiently understood. The purpose of the present study was to investigate the potential relationship between IL-36γ and HT. We included 100 subjects, among whom, 52 had early-stage HT and 48 were healthy controls (HC). The subjects' basic clinical information was obtained through physical examination and clinical histories of signs and symptoms. Thyroid function and measurements of thyroid-stimulating hormone (TSH), free triiodothyronine 3, free triiodothyronine 4 (FT4), thyroid peroxidase antibody (TPO-Ab), and thyroid globulin antibody were measured using a fully automated chemiluminescent immunoassay analyzer. The expression levels of serum IL‐36γ were determined using an enzyme-linked immunosorbent assay. The serum IL-36γ level in the HT group was significantly higher compared with that of the HC group [91.91 (67.52, 130.90) pg/mL vs 62.50 (44.61, 91.53) pg/mL, P < 0.0001]. Correlation analysis showed a negative correlation between serum IL-36γ and TPO-Ab titers in the HT group (r = -0.3507, P = 0.0054). According to receiver operating characteristic curve analysis, the area under the curve (AUC) for IL-36γ was 0.7278 (P < 0.0001), and the AUC for IL-36γ combined with TSH and FT4 was 0.8109 (P < 0.0001). The present study indicates that serum IL-36γ expression is increased in patients with HT and negatively correlates with TPO-Ab. Our findings suggest that IL-36γ may be involved in the development of HT and may therefore serve as a potential new diagnostic biomarker for HT. [ABSTRACT FROM AUTHOR]

• A case of hyperchylomicronemia caused by GPIHBP1 autoantibodies. • Transformation of Hashimoto's thyroiditis to Basedow's disease. • Fluctuating thyroid autoimmune disease. • GPIHBP1 autoantibodies are not always persistent, but intermittent. Recent studies have reported that patients with autoimmune hyperchylomicronemia caused by glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) autoantibodies are associated with rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, Hashimoto's thyroiditis, Basedow's disease, and immune thrombocytopenia. We report a rare case of hyperchylomicronemia due to GPIHBP1 autoantibodies and fluctuating thyroid autoimmune disease. A 28-year-old woman, diagnosed with Hashimoto's thyroiditis at 26 years of age, started taking 50 µg/day of levothyroxine sodium. She had an episode of acute pancreatitis at 27 years of age; her serum triglyceride (TG) level was 1291 mg/dL at that time. The patient was referred to our hospital because her hyperchylomicronemia (hypertriglyceridemia) did not improve on treatment with pemafibrate and eicosapentaenoic acid (EPA). Serum total cholesterol and TG levels were 237 mg/dL and 2535 mg/dL, respectively, while plasma pre-heparin lipoprotein lipase (LPL) mass was 15 ng/mL (26.5-105.5 ng/mL). We diagnosed her as Basedow's disease based on autoimmune antibodies and ultrasound examination. Targeted exome sequencing revealed no pathogenic variants in the LPL or GPIHBP1 genes. The serum GPIHBP1 autoantibody level was 686.0 U/mL (<58.4 U/mL) and GPIHBP1 mass was 301.9 pg/mL (570.6-1625.6 pg/mL). The patient showed hyperchylomicronemia during periods of hypothyroidism and hyperthyroidism, whereas GPIHBP1 autoantibodies were positive during episode of hyperchylomicronemia but negative during periods of normal TG levels. Based on these findings, the patient was diagnosed with hyperchylomicronemia due to GPIHBP1 autoantibodies and treated with rituximab. GPIHBP1 autoantibodies remained undetectable and TG levels were controlled at approximately 200 mg/dL. [ABSTRACT FROM AUTHOR]

• Revealing a potential link between papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT). • Identification of potential biomarkers associated with HT and PTC. • Multi-level validation approaches. • PI3K-Akt and immunology connections play potential regulatory role. • Laying the foundation for future research and clinical applications. Hashimoto's thyroiditis (HT) is widely recognized as a risk factor for papillary thyroid carcinoma (PTC). This study aimed to identify key targets involved in the progression of HT to PTC. Microarray datasets (GSE138198) for PTC, HT, and PTC with HT in the background (PTC-W) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and analyzed between normal and diseased groups. Functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction (PPI) network analysis was conducted to identify hub genes, which were validated through qPCR and immunohistochemical (IHC) analysis. ROC analysis was then carried out based on the expression levels of hub genes in clinical plasma samples. A total of 78 shared DEGs were identified from the GEO dataset. GO and KEGG analyses highlighted pathways such as epithelial-to-mesenchymal transition (EMT) and PI3K-Akt signaling. The analysis of immune cell subtypes showed that the hub genes were commonly associated with various immune cells, particularly dendritic cells (DC) and macrophages. Ten hub genes—LYZ, FCER1G, CCL18, CXCL9, ALOX5, TYROBP, C1QB, CTSS, MET, and FAM20A—were identified from the PPI network. qPCR and IHC confirmed the overexpression of MET and FAM20A in PTC-W. The area under the curve (AUC) of the ROC analysis was 0.889 for MET and 0.825 for FAM20A. This study identified two hub genes, MET and FAM20A, with potential diagnostic value in HT and PTC. [ABSTRACT FROM AUTHOR]

• Heterogeneity of integrin expressed on B cells in thyroid and circulation in AITD. • Circulating α4β7+ and α4β1+ B cells correlate with thyroid function and TSI in GD. • Intrathyroidal α4β1+ B cells exhibit positive association with TSH levels in HT. • Intrathyroidal α4β7+ B cells and α4β1+ B cells correlate with elevated zonulin in HT. Integrins are upregulated on endothelial cells and T-lymphocytes in autoimmune thyroid disease (AITD), potentially contributing to immune response localization. The role of integrins on B-cells in AITD remains unclear. Peripheral blood samples were collected from healthy controls (n = 56), patients with Graves' disease (GD) (n = 37) and Hashimoto's thyroiditis (HT) (n = 52). Ultrasound-guided fine-needle aspiration (FNA) of the thyroid was performed in patients with non-autoimmune thyroid disease (nAITD) (n = 19), GD (n = 11), and HT (n = 40). Integrins α4β7, α4β1, and αEβ7 in B cells were measured by flow cytometry. Serum zonulin levels were quantified via ELISA. Associations of integrins on B cells with thyroid hormones, thyroid autoantibodies, AITD duration, and zonulin were analyzed. HT patients exhibited lower α4β7 and higher α4β1 expression on B cells compared to healthy controls and GD patients. While α4β7 was predominant on circulating B cells, the dominant integrin expressed on intrathyroidal B cells varied with specific thyroid diseases. In GD patients, α4β7 and α4β1 expression on circulating B cells correlated positively and negatively with thyroid function and thyroid stimulating immunoglobulins (TSI) levels, respectively. Intrathyroidal α4β1+ B cells positively correlated with TSH levels in HT patients. Additionally, serum zonulin was elevated in HT patients, and intrathyroidal α4β7+ B cells and α4β1+ B cells correlated negatively and positively with zonulin levels, respectively. Integrin αEβ7 on B cells showed no significant association with AITD. Integrins expressed on B cells potentially play a role in the pathogenesis of AITD and might serve as immune biomarkers for the disease. [ABSTRACT FROM AUTHOR]

• Programmed cell death pathways were found to be enriched in dendritic cells within the thyroid tissue in Hashimoto's thyroiditis. • TNFAIP3, CYBB, PTPN6, STAT1, TGFB1, and NLRP3 are enriched on dendritic cells and positively correlate with TPOAb and TGAb. • CASP8 was found to be involved in regulating various cell death processes in Hashimoto's thyroiditis. Hashimoto's thyroiditis (HT) is a chronic autoimmune disorder. As antigen-presenting cells, dendritic cells(DCs) play a pivotal role in inducing programmed cell death (PCD) types, contributing to immune disorders. This study aimed to identify genes associated with multiple PCD pathways in dendritic cells within the thyroid tissue of patients with HT. The single-cell RNA-sequencing dataset HRA001684 was obtained from the National Genomics Data Center (NGDC) to calculate the area under the curve (AUC) scores for PCD-related genes. Additionally, mRNA sequencing datasets GSE138198 and HRA001684 were sourced from the Gene Expression Omnibus(GEO) and NGDC, respectively. Differentially expressed genes (DEGs) were identified by comparing normal and HT groups in GSE138198 and HRA001684. The intersection of these DEGs with PCD-related genes led to the identification of 17 PCD-related DEGs(PCDDEGs). AUC scores revealed that DCs in HT exhibited significantly elevated levels of necroptosis, ferroptosis, pyroptosis, autophagy, and PANoptosis, expressing six key PCDDEGs: TNFAIP3 , CYBB , PTPN6 , STAT1 , TGFB1 , and NLRP3. These genes displayed an AUC>0.8 for HT in the GSE29315, GSE138198, and HRA001684 datasets, confirming their diagnostic accuracy. Moreover, their expression was positively correlated with the serum levels of thyroid peroxidase and thyroglobulin antibodies, while the expression of all PCDDEGs was negatively correlated with the abundance of thyroid follicular epithelial cells. qRT-PCR, WB, IHC, and IF experiments further confirmed the differences in PCDDEGs gene and protein levels in HT patients. These findings highlight the crucial role of DCs in mediating PCD within the thyroid tissues of HT patients. The identified PCDDEGs— TNFAIP3 , CYBB , PTPN6 , STAT1 , TGFB1 , and NLRP3— may significantly contribute to HT pathogenesis through PCD pathways. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis is a chronic autoimmune inflammatory disease with a high prevalence and currently lacks effective treatment options. Previous preclinical and clinical trials have established mesenchymal stem cells (MSCs) as a promising therapeutic approach; however, there is limited research on MSC treatment for Hashimoto's thyroiditis, and the underlying molecular mechanisms remain unclear. MSCs isolated from 4 to 6-week-old Lewis rats were employed for thyroiditis treatment. The efficacy of MSCs was assessed through histological and serological parameters. Molecular mechanisms of MSC therapy for Hashimoto's thyroiditis were explored by examining macrophage presence within thyroid tissue and relevant pathways. In this study, we observed elevated oxidative stress and endoplasmic reticulum stress within the thyroid tissue of Hashimoto's thyroiditis patients, and MSC therapy effectively mitigated this process. Furthermore, we found that the therapeutic potential of MSCs in the EAT model depended on the STING pathway. MSCs reduced endoplasmic reticulum stress and inflammasome levels within the thyroid tissue by modulating the STING pathway. Additionally, MSCs inhibited the expression of IRE1α in thyroid tissue macrophages, thereby reducing the polarization of M1-type macrophages The STING pathway appears to be a crucial mechanism by which MSCs modulate macrophage polarization in thyroid tissue, offering a potential treatment for thyroiditis. [Display omitted] • MSCs show promise in treating autoimmune thyroiditis. • MSCs impact the STING pathway, reducing oxidative stress in thyroid tissue. • MSCs lower IRE1α in macrophages, decreasing harmful M1 polarization. • Highlights MSCs as a novel therapy for Hashimoto's, supporting new treatment strategies. • Enhances understanding of macrophage roles in Hashimoto's pathophysiology. [ABSTRACT FROM AUTHOR]

Recent studies have confirmed that B cell-related genes CD20 and FCRL5 may be involved in the pathogenesis of autoimmune thyroid diseases (AITDs). However, there is a lack of comprehensive genetic susceptibility studies on this subject. The purpose of this study was to investigate the relationship of CD20 and FCRL5 gene polymorphisms with AITD susceptibility. A total of 1740 subjects were recruited from the Chinese Han population. They consisted of 1007 patients with AITD and 633 healthy controls. Multiplex polymerase chain reaction (PCR) combined with high-throughput sequencing was used to genotype four screened single nucleotide polymorphisms (SNPs). The four SNPs were rs7126354 of CD20 and rs6667109, rs6692977 and rs3811035 of FCRL5. The minor allele frequency of rs7126354 was significantly lower in patients with AITD and Hashimoto's thyroiditis (HT) than in healthy controls (P = 0.031; P = 0.017). The minor allele frequency of rs6667109 was significantly higher in the Graves' disease (GD) subgroup than in the healthy control group (P = 0.029). In the Log-additive model, rs6667109 in the GD group also showed an increased risk of onset disease. This study presents robust evidence of a genetic association of CD20 and FCRL5 with AITDs. The C allele of CD20 rs7126354 is a protective factor for HT susceptibility. The A allele of FCRL5 rs6667109 is a risk factor for the susceptibility to GD. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are a group of disorders characterized by abnormal immune responses that mistakenly target and attack healthy cells, tissues, and organs, resulting in inflammation and tissue damage. Omega-3 fatty acids possess anti-inflammatory activities and may decrease abnormal immune activity. However, the role of omega-3 fatty acids in various autoimmune diseases is still unclear. This umbrella review and Mendelian randomization (MR) study aims to summarize the highest available evidence on omega-3 fatty acids and autoimmune disease. We conducted an umbrella review by searching electronic databases to identify systematic reviews and meta-analyses. The selection criteria included systematic reviews with or without meta-analysis, which evaluated omega-3 fatty acids as the exposure and autoimmune disease as the outcome variable. Two authors independently assessed the overlapping and quality of the reviews using the AMSTAR-2 tool. We also performed MR studies to investigate the potential causal effect of fatty acids on the risk of various autoimmune diseases, utilizing data from the meta-analysis of the UKB-TOPMed and FinnGen cohorts. The umbrella review identified 21 studies (8 systematic reviews and 13 meta-analyses) on 9 autoimmune diseases and 30 diseases in the MR study. AMSTAR 2 categorized the quality of evidence in six studies as critically low, six studies as low, eight studies as moderate, and one as high-quality evidence. The consistent result between the review and the MR study demonstrated the benefit of omega-3 fatty acids on rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Additionally, in our summary review, omega-3 fatty acids can improve disease activity and inflammation biomarkers; however, MR studies provided no consistent evidence for the causal effects of omega-3 fatty acids on psoriasis, multiple sclerosis (MS), type 1 diabetes (T1D), IgA nephropathy (IgAN), juvenile idiopathic arthritis (JIA), Crohn's disease (CD), and ulcerative colitis (UC). The current study presented solid evidence highlighting the advantageous impact of omega-3 fatty acids on SLE and RA. This was achieved through the reduction of disease risk, the decrease of disease activity, and the mitigation of inflammatory biomarkers. To stratify another autoimmune illness, it is necessary to carry out rigorous evaluations to surpass the existing findings and enhance understanding in this domain. [Display omitted] • Omega-3 fatty acids reduce disease risk, activity, and inflammation in SLE and RA • Omega-3 fatty acids show potential benefits for autoimmune diseases such as psoriasis, type 1 diabetes, multiple sclerosis, juvenile arthritis, IgA nephropathy, Crohn's disease, and ulcerative colitis. • Higher genetically predicted omega-6, LA, omega-6/omega-3 ratio levels, and MUFA are associated with an increased risk of autoimmune diseases such as RA, SLE, autoimmune thyroiditis, and alopecia areata. [ABSTRACT FROM AUTHOR]

• Vitamin D administration significantly decreased thyroid follicle destruction, lymphocyte infiltration, and lowered serum levels of thyroid hormones and autoantibodies. • Vitamin D treatment effectively reduced Th17 cell frequencies while promoting the Treg cell subsets both in vivo and in vitro. • Vitamin D suppressed pro-inflammatory while facilitating anti-inflammatory cytokines production. • Vitamin D enhanced YAP expression and activated the JAK/STAT pathway. Autoimmune thyroiditis (AITD) is an organ-specific autoimmune disease. Substantial evidence suggests that Vitamin D (VitD) deficiency is closely associated with an increased risk of AITD. However, the effects of VitD3 on immune cells, especially Th17/Treg cell subsets, and the underlying molecular mechanism in AITD have not yet been investigated. An experimental autoimmune thyroiditis (EAT) mouse model was established with a high-iodine diet. After 8 weeks, thyroid injury was assessed using hematoxylin and eosin (H&E) staining. ELISA was employed to measure serum levels of thyroxine (T3 and T4), thyroid autoimmune antibodies (Tg-Ab and TPO-Ab), and inflammatory cytokines. Flow cytometry and multiplex fluorescence immunohistochemical (mIHC) assays were used to analyze Th17/Treg cell subsets. The CCK-8 and flow cytometry assays were used to determine cell viability and apoptosis. Administration of VitD3 reduced thyroid follicle destruction, decreased lymphocyte infiltration, and lowered T3, T4, Tg-Ab, and TPO-Ab serum levels in EAT mice. VitD3 treatment also reduced the frequency of Th17 cells while promoting the Treg cell subset both in the thyroid tissue and in the splenocytes cultured in vitro. Furthermore, VitD3 administration suppressed the production of inflammatory cytokines in EAT mice. VitD3 was also found to regulate Treg cells' differentiation, viability, and apoptosis. Mechanistically, we discovered that VitD3 treatment upregulated YAP expression and activated the JAK/STAT pathway. Rescue assays confirmed that depletion of YAP counteracted the effects of VitD3 on Treg cell differentiation and function. Vitamin D3 attenuates AITD by modulating Th17/Treg cell balance via regulating the YAP/JAK1/STAT1 axis. [ABSTRACT FROM AUTHOR]

Recently, large pretrained vision foundation models based on masked image modeling (MIM) have attracted unprecedented attention and achieved remarkable performance across various tasks. However, the study of MIM for ultrasound imaging remains relatively unexplored, and most importantly, current MIM approaches fail to account for the gap between natural images and ultrasound, as well as the intrinsic imaging characteristics of the ultrasound modality, such as the high noise-to-signal ratio. In this paper, motivated by the unique high noise-to-signal ratio property in ultrasound, we propose a deblurring MIM approach specialized to ultrasound, which incorporates a deblurring task into the pretraining proxy task. The incorporation of deblurring facilitates the pretraining to better recover the subtle details within ultrasound images that are vital for subsequent downstream analysis. Furthermore, we employ a multi-scale hierarchical encoder to extract both local and global contextual cues for improved performance, especially on pixel-wise tasks such as segmentation. We conduct extensive experiments involving 280,000 ultrasound images for the pretraining and evaluate the downstream transfer performance of the pretrained model on various disease diagnoses (nodule, Hashimoto's thyroiditis) and task types (classification, segmentation). The experimental results demonstrate the efficacy of the proposed deblurring MIM, achieving state-of-the-art performance across a wide range of downstream tasks and datasets. Overall, our work highlights the potential of deblurring MIM for ultrasound image analysis, presenting an ultrasound-specific vision foundation model. • We propose a specialized deblurring masked image modeling (MIM) approach tailored for ultrasound image analysis by incorporating a deblurring task into the pretraining proxy task. • We utilize a multi-scale hierarchical encoder architecture, enabling the extraction of both fine- and coarse-grained image representations. • We conduct pretraining experiments on 280,000 thyroid ultrasound images, and the downstream tasks encompass various disease diagnoses (nodule and Hashimoto's thyroiditis), as well as different types of tasks (classification and segmentation). • As the first MIM-based work for ultrasound, we delve into fundamental considerations for modality-specific foundation models, yielding significant conclusions. [ABSTRACT FROM AUTHOR]

The habitual intake of selenium (Se) varies strongly around the world, and many people are at risk of inadequate supply and health risks from Se deficiency. Within the human organism, efficient transport mechanisms ensure that organs with a high demand and relevance for reproduction and survival are preferentially supplied. To this end, selenoprotein P (SELENOP) is synthesized in the liver and mediates Se transport to essential tissues such as the endocrine glands and the brain, where the "SELENOP cycle" maintains a privileged Se status. Mouse models indicate that SELENOP is not essential for life, as supplemental Se supply was capable of preventing the development of severe symptoms. However, knockout mice died under limiting supply, arguing for an essential role of SELENOP in Se deficiency. Many clinical studies support this notion, pointing to close links between health risks and low SELENOP levels. Accordingly, circulating SELENOP concentrations serve as a functional biomarker of Se supply, at least until a saturated status is achieved and SELENOP levels reach a plateau. Upon toxic intake, a further increase in SELENOP is observed, i.e., SELENOP provides information about possible selenosis. The SELENOP transcripts predict an insertion of ten selenocysteine residues. However, the decoding is imperfect, and not all these positions are ultimately occupied by selenocysteine. In addition to the selenocysteine residues near the C-terminus, one selenocysteine resides central within an enzyme-like environment. SELENOP proved capable of catalyzing peroxide degradation in vitro and protecting e.g. LDL particles from oxidation. An enzymatic activity in the intact organism is unclear, but an increasing number of clinical studies provides evidence for a direct involvement of SELENOP-dependent Se transport as an important and modifiable risk factor of disease. This interaction is particularly strong for cardiovascular and critical disease including COVID-19, cancer at various sites and autoimmune thyroiditis. This review briefly highlights the links between the growing knowledge of Se in health and disease over the last 50 years and the specific advances that have been made in our understanding of the physiological and clinical contribution of SELENOP to the current picture. [Display omitted] • Selenoprotein P (SELENOP) in the blood has transport functions to target tissues. • SELENOP protects certain tissues from Se loss in deficiency via SELENOP cycling. • SELENOP binds heavy metals and heparin with unclear physiological significance. • Enzymatic activity of SELENOP is described in vitro, while clinical evidence is lacking. • SELENOP concentrations and autoantibodies to SELENOP associate with health risks. [ABSTRACT FROM AUTHOR]

The signaling pathway centered on the transcription factor nuclear erythroid factor 2-like 2 (Nrf2) has emerged during the last 15 years as a target for the prevention and treatment of diseases broadly related with oxidative stress such as cancer, neurodegenerative and metabolic diseases. The roles of Nrf2 are expanding beyond general cytoprotection, and they encompass its crosstalk with other pathways as well as tissue-specific functions. The thyroid gland relies on reactive oxygen species for its main physiological function, the synthesis and secretion of thyroid hormones. A few years ago, Nrf2 was characterized as a central regulator of the antioxidant response in the thyroid, as well as of the transcription and processing of thyroglobulin, the major thyroidal protein that serves as the substrate for thyroid hormone synthesis. Herein, we summarize the current knowledge about the roles of Nrf2 in thyroid physiology, pathophysiology and disease. We focus specifically on the most recent publications in the field, and we discuss the implications for the preclinical and clinical use of Nrf2 modulators. [Display omitted] • The thyroid gland is among the human tissues with the highest expression levels of NRF2 and its target gene NQO1. • NRF2 regulates the antioxidant and cytoprotective response in the thyroid.Deletion of Nrf2 in mice decreases the thyroidal abundance of thyroglobulin (Tg) but increases the abundance of iodinated Tg. • Mice with decreased Keap1 expression present increased Tg degradation, age-dependent goiter and subclinical hypothyroidism. • Germline and somatic mutations in KEAP1 have been observed in patients with goiter and thyroid cancer, respectively. • NFE2L2 promoter SNPs interact genetically with a selenocystein system to modulate the risk of Hashimoto's thyroiditis. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis (HT) is one of the commonest autoimmune disorders. This study was performed to investigate the potential effect of histone deacetylase 6-specific inhibitor (HDAC6i) on Th17 cell differentiation in animal model and the underlying mechanism. Experimental autoimmune thyroiditis (EAT) mouse model was established by subcutaneously immunization of porcine thyroglobulin (pTg) and adjuvant, and the HDACi Tubastatin A (TSA) or HDAC6i (ACY-1215) was intraperitoneally injected into mice in the following. The histological examination and immune analysis in EAT mice were carried out. Next, the CD4+ T cells were isolated from peripheral blood mononuclear cells (PBMCs) of EAT mice followed by Th17 cell differentiation assay. The associated factor levels, and the protein interaction between HDAC6 and PKM2 were examined. Subsequently, the effect of STAT3 activation on Th17 cell differentiation was explored. ACY-1215 or TSA treatment reduced lymphocytic infiltration and alleviated thyroid tissue injury in EAT mice. Correspondingly, either ACY-1215 or TSA treatment reduced the levels of anti-thyroglobulin (Tg), anti-thyroid peroxidase (TPO), IL-17A, and IFN-γ in the serum, decreased Th17 cell differentiation, but enhanced TGF-β level and promoted Treg cell differentiation. In vitro, after induction of Th17 cell differentiation from CD4+ T cells, HDAC6 activity and Th17 cell differentiation were significantly decreased when treated with ACY-1215 or TSA. HDAC6 could interact with PKM2, and HDAC6 overexpression promoted the phosphorylation of STAT3 and PKM2 nuclear translocation. Furthermore, the STAT3 activator treatment reversed the effects of ACY-1215 or TSA treatment. HDAC6i suppresses Th17 cell differentiation and attenuates HT via PKM2/STAT3 axis. • HDAC6-specific inhibitor alleviated pathological injury of HI. • HDAC6 mediates the deacetylation of PKM2 and its nuclear translocation. • HDAC6-specific inhibitor reduced differentiation of Th17 cells via regulating PKM2/STAT3 axis. [ABSTRACT FROM AUTHOR]

Patients with type 1 diabetes (T1D) are more likely to develop other autoimmune diseases than the general population. To describe additional autoimmunity in a cohort of children and adolescents with T1D, as well as to identify factors associated with the presence of additional autoantibodies (AABs) and of additional autoimmune diseases (AADs). This was a single-center retrospective cohort study of 179 children and adolescents (median age: 9.1 years) diagnosed with T1D between 2014 and 2020 in a specialized center in France. Patients were screened for autoimmune thyroiditis and celiac disease at T1D diagnosis and once every 1–2 years during follow-up. Other AADs and their specific autoantibodies were screened for only if clinical or laboratory signs were present. At T1D diagnosis, 15.6% of participants presented with at least one type of AAB including antibodies specific to Hashimoto's disease (TPOAb and/or TGAb) and/or to celiac disease (tTGAb and/or EMAb). Only 2.8% of participants presented with an AAD as early as T1D diagnosis. The median follow-up was 37 months. The cumulative incidence of AABs and AADs at 2 years of follow-up was, respectively, 3.9% and 5.4%, and it doubled at 3 years of follow-up. Only one patient, also affected by Down syndrome, was diagnosed with 2 AADs. Hashimoto's disease was the most frequently diagnosed AAD, followed by celiac disease, both at an asymptomatic stage. Vitiligo and Graves' disease were also diagnosed in this cohort but affected few patients. Children aged 6–12 years were more likely to present with an AAD at diabetes diagnosis (p = 0.043). : The high prevalence and incidence of additional autoimmunity in children and adolescents with T1D justifies regular screening of AABs and AADs. [ABSTRACT FROM AUTHOR]

Background: Long-term neuropsychiatric sequelae of autoimmune encephalitis (AE) remain understudied, particularly in pediatric-onset AE. We aimed to synthesize the published data on ongoing psychiatric symptoms in pediatric-onset AE.Methods: The Pubmed, PyscINFO, Web of Science databases were searched from their inception years to August 23, 2021, and 29 studies were identified and analyzed. We also performed a quantitative synthesis of available patient data from the 29 studies combined with a cohort of anti-NMDA receptor (NMDAR) AE from our institution to examine the associations between acute treatment course and long-term psychiatric outcome.Results: At long-term follow up, 52.4% of the cases with pediatric-onset AE had any persistent symptom and 36.0% had at least one psychiatric symptom. Pooled data found that 36.3% of pediatric-onset anti-NMDAR AE had ongoing psychiatric symptoms. Using a univariate logistic regression analysis, we found that abnormal initial EEG, use of certain immunotherapies, and persistent cognitive impairments were associated with ongoing psychiatric symptoms.Limitations: Limitations of the existing literature included a significant paucity of outcomes measured using consistent, objective methods. Limitations of the systematic review included the wide variability among the studies reviewed, which rendered a meta-analysis impossible and beyond the scope of the paper.Conclusion: Chronic psychiatric and behavioral problems remain present in one-third of children months to years after onset of AE. Larger scaled prospective observational studies with a consistent standardized battery of testing are needed to examine impact of specific clinical features and immunotherapies on long-term mental health outcomes. [ABSTRACT FROM AUTHOR]

Autoimmune thyroid diseases (AITD), a group of prevalent and persistent immune-mediated disorders affecting the endocrine system, can progressively result in total thyroid failure, thereby drastically impacting metabolic processes. Given the inadequacies of current clinical approaches to managing AITD, The exigency to investigate novel therapeutic strategies demands immediate attention, given the limitations and potential resistances associated with conventional approaches. Si-Ni-San (SNS), first chronicled in the esteemed Eastern Han Dynasty medical text " Treatise on Cold Damage and Miscellaneous Diseases" circa 200-210 AD, is a time-honored remedy known for its harmonizing effects on the liver and invigorating properties for the spleen. Research indicates that saikosaponins and peony glycosides, two primary constituents of SNS, possess anti-inflammatory properties and can ameliorate immune dysfunction in the treatment of AITD. Despite initial insights, a comprehensive exploration of the underlying mechanisms by which SNS alleviates AITD symptoms requires further in-depth investigation to decipher their intricate interplay. This study aimed to identify the key therapeutic components of SNS for the treatment of AITD and to elucidate the underlying molecular mechanisms, revealing potential targets. We initially screened prospective components of SNS for AITD therapy through comprehensive database exploration, followed by an evaluation of the results via PPI networks. To illuminate the therapeutic mechanisms of SNS in AITD, we employed GO enrichment analysis and surveyed the KEGG pathways. Employing UHPLC-QE-MS, we conducted an in-depth analysis of SNS's principal elements, complemented by molecular docking studies to unravel their interaction dynamics. Finally, we substantiated the central therapeutic pathway of SNS in the treatment of AITD using an experimental autoimmune thyroiditis (EAT) mouse model, validated meticulously through in vivo experimentation. Network pharmacology analysis revealed 32 common targets from the overlap between SNS and AITD-related targets. Based on subsequent PPI network and KEGG analysis, we focused on the IL-6/JAK2/STAT3/IL-17 pathway, which drives the differentiation of Th17 cells, as a central therapeutic target of SNS in AITD. Crucially, our in vivo findings, substantiated through immunohistochemical, Western blot, RT-qPCR analyses and Flow cytometry analysis, reveal SNS's therapeutic potential in AITD. It effectively dampens IL-6 production, inhibits IL-6/JAK2/STAT3/IL-17 pathway activation, and rebalances the Th17/Treg cell ratio, thus elucidating its anti-inflammatory mechanism. The protective effect of SNS against AITD is likely mediated through the modulation of the IL-6/JAK2/STAT3/IL-17 pathway and the restoration of balance within the Th17/Treg ratio. This suggests that SNS may exert its therapeutic effects on AITD by targeting these key molecular mechanisms, thereby providing a novel perspective for the treatment of AITD. [Display omitted] • Si-Ni-San（SNS） can significantly improve thyroid autoimmune injury in EAT mice. • SNS can reduce the lymphocyte infiltration in thyroid tissue and the content of inflammatory cytokines in blood of EAT mice. • SNS restored the balance between Th17/Treg cells. • SNS inhibited the activation of IL-6/JAK2/STAT3/Th17 pathway and reduced the differentiation of Th17 cell. [ABSTRACT FROM AUTHOR]

Autoimmune thyroid diseases (AITD) often interfere with early detection due to asymptomatic symptoms and normal thyroid function in routine tests. Developing early diagnostic tools is crucial for timely and accurate treatment, potentially reducing complications and improving patient outcomes. In this study, we developed Ox-NE, a novel fluorescent probe designed for the specific detection and quantification of neutrophil elastase (NE), a key biomarker of inflammation. Unlike the traditional probes, Ox-NE utilizes a unique mechanism that minimizes background fluorescence and enhances photostability, offering rapid, non-invasive, and apparent diagnostic capabilities. Ox-NE had a low limit of detection (LOD) of 1.54 μg/mL and exhibited high sensitivity and specificity with strong anti-interference properties. Through in vitro experiments, Ox-NE could accurately detect elevated NE levels in the serum of thyroiditis patients. Additionally, it could differentiate between normal thyroid cells, inflamed thyroid cells, and thyroid cancer cells. It also effectively facilitated the screening of sivelestat, a therapeutic agent for thyroiditis. Successful fluorescence imaging in mouse models further confirmed the potential of Ox-NE in advancing thyroid disease diagnostics. [Display omitted] • Ox-NE is the first non-conjugated organic probe to detect autoimmune thyroiditis, effectively reducing high background signals. • Ox-NE could effectively distinguish between thyroid inflammation and thyroid cancer. • NE shows potential as a clinical biomarker of serum in thyroid diseases, with Ox-NTR as a promising diagnostic imaging tool. [ABSTRACT FROM AUTHOR]

[Display omitted] • Irisin linked to thyroid function in metabolic diseases. • Complex irisin-thyroid relationship explored in research review. • Serum irisin studies aim to guide future clinical trials. Irisin, a hormone-like adipo-myokine, has garnered considerable attention in recent years for its potential impact in metabolic diseases. Its physiological effects are similar to those of thyroid hormones, prompting numerous investigations into potential correlations and interactions between irisin and thyroid function through various in vitro and animal experiments. However, existing studies suggest that the relationship between irisin and thyroid diseases is highly complex and multifaceted. In this paper, we have summarized the research results on serum irisin and thyroid function, providing an overview of advancements and constraints in current research on irisin and thyroid hormones. The aim is to offer insights and directions for future clinical trials in this field. [ABSTRACT FROM AUTHOR]

The T-cell receptor (TCR)/CD3 complex plays a crucial role in T-cell development and immune regulation. CD3G gene encodes one of the CD3 subunits named CD3γ, and its deficiency can cause autoimmune disorders, immunodeficiency and recurrent infections. To date, only 13 patients with CD3G variants have been reported. We report a 10-year-old Chinese boy presented with lupus-like disease in addition to autoimmune thyroiditis, asthma, immunodeficiency and recurrent infection. Flow cytometric analysis revealed apparently decreased levels of CD3+ and CD8+ T cells but mildly decreased CD4+ T cells. However, the activation of T cells and B cells increased. Trio-based whole-exome sequencing revealed a homozygous pathogenic variant (c.213delA, p.Lys71fs) of CD3G gene in the proband. His parents were both heterozygous carriers of this variant. This is the first patient who met the diagnostic criteria for systemic lupus erythematosus by the Systemic Lupus International Collaborating Clinics (SLICC) group. In addition to low T cells and low Treg cells, our study further revealed T cells and B cells activation enhanced in CD3γ deficiency patient, which may play an important role in autoimmunity. We believe that our study makes a significant contribution to the literature and will provide further insight into CD3γ deficiency and monogenic lupus. [ABSTRACT FROM AUTHOR]

[Display omitted] • This article provided a thorough summary of genetic variations linked to a higher susceptibility to autoimmune thyroid diseases (AITD). • Susceptibility genes significantly affected immune system regulation and response, potentially triggering AITD onset. • Susceptibility genes emerged as essential markers for the diagnosis, treatment, and prognosis of AITD. Autoimmune thyroid diseases (AITDs), including Graves' disease and Hashimoto's thyroiditis, are organ-specific autoimmune disorders characterized by conditions including goiter, autoimmune thyroiditis, hyperthyroidism, and hypothyroidism, which represent the most severe clinical manifestations of AITDs. The prevalence of autoimmune thyroid disorders is on the rise, influenced by increased environmental factors and changes in modern lifestyles. Understanding the pathophysiology of AITDs is crucial for identifying key factors that affect the disease's onset, progression, and recurrence, thereby laying a solid foundation for precise diagnosis and treatment. The development of AITDs involves a complex interplay of environmental influences, immune dysfunctions, and genetic predispositions. Genetic predispositions, in particular, are significant, with numerous genes identified as being linked to AITDs. This article focuses on examining the genes vulnerable to AITDs to deepen our understanding of the relevant genetic contributors, ultimately facilitating the development of effective prevention and treatment methods. [ABSTRACT FROM AUTHOR]

Autoimmunity refers to the presence of autoantibodies and autoreactive lymphocytes against the structural molecules of an individual's cells or tissues, known as self-antigens or autoantigens. It might exist in the absence of autoimmune disease. However, how autoimmunity develops remains a mystery, despite the discovery of autoantibodies in human cord blood. Murine fetuses on day 14 of gestation were subjected to intraperitoneal injection of murine thyroid peroxidase (TPO) peptides or collagen type II (CII) at graded doses via transuterine approach. Postnatally, the recipients were examined for autoantibodies by ELISA and autoreactive lymphocytes by in vitro incorporation of tritium and for the development of autoimmune thyroiditis or arthritis. At one month of age, the recipients did not secrete significant levels of anti-TPO or CII IgG 2a in sera until a dose of 0.5 µg TPO or 5.0 µg CII was injected in utero. Serum anti-TPO or CII IgG 2a persisted for at least two to four months postnatally. In recipients with elevated autoantibodies, their lymphocytes also showed proliferative responses specifically to TPO or CII. However, the development of autoantibodies and autoreactive lymphocytes was not associated with inflammatory cell infiltration of thyroid glands or paw joints even though anti-TPO or CII IgG 2a was enhanced by postnatal TPO or CII challenge. Fetal exposure to free autoantigens could be immunogenic, shedding new light on the in utero origin of autoantibodies and autoreactive lymphocytes. The development of autoimmunity requires a threshold intensity of autoantigen exposure in the fetus. [ABSTRACT FROM AUTHOR]

Aim: To analyse the clinicopathological features and ultrasound findings of the diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) and compare differences between children/adolescents (CAs) and adults.Materials and Methods: Medical records and ultrasound images of 97 consecutive DSV-PTC patients were reviewed and comparison was made between CAs and adults.Results: The average age was 31.2 ± 12.4 years old and 16.5% patients were CAs. Unilateral lobe was involved in 40.2% patients and 69.1% combined with Hashimoto's thyroiditis. Up to 95.9% patients had lymph node metastasis (LNM). CAs had more contralateral central LNM (CCLNM) and contralateral lateral LNM (CLLNM) than adults (p=0.047, p=0.025). Lung metastasis was also more common in CAs (p=0.002). Involved lobes mostly appeared as diffuse heterogeneous echogenicity on ultrasonography with isoechogenicity as the most common predominant echo (48.4%). Diffuse microcalcifications were observed frequently with grade 2-3 accounting for 52.3%. Lesions involving the whole gland lobe (diffuse type) occurred in 63.9%. Blood flow was poor in 71.6% (with grade 0-1). Microcalcifications of both lobes and metastatic lymph nodes and lesions involving (diffuse type) were more common in CAs (p=0.038, 0.002; 0.011). Of 39 patients with unilateral lobe involvement, ultrasonic sensitivity for CCLNM and CLLNM was only 50% and 66.7% respectively.Conclusion: DSV-PTC has characteristic ultrasonographic findings. DSV-PTC of CAs may be more aggressive than that of adults. Ultrasonic sensitivity for LNM of contralateral compartments was not satisfactory and diagnostic methods with good efficacy are required. [ABSTRACT FROM AUTHOR]

• Diagnostic accuracy of a new fully automated TSI immunoassay (Immulite™ TSI assay) in GD patients. • Comparing Immulite™ TSI assay to the third generation thyroid-stimulating hormone receptor antibody (TRAb) electrochemiluminescence assay (Elecsys Anti-TSHR assay). • Clinical characteristics associated with responsiveness to methimazole in patients with newly diagnosed GD. As thyroid-stimulating immunoglobulins (TSI) are a sign of Graves' disease (GD), measuring TSI titers is becoming increasingly important for GD diagnosis. This study evaluated the diagnostic accuracy of a new fully automated TSI immunoassay (Immulite™ TSI assay) in GD patients and compared it to the third generation thyroid-stimulating hormone receptor antibody (TRAb) electrochemiluminescence assay (Elecsys Anti-TSHR assay). Additionally, clinical characteristics associated with responsiveness to methimazole in patients with newly diagnosed GD were preliminarily explored. This study involved 324 subjects, comprising patients with untreated GD (GD-UT), Graves' ophthalmopathy (GO) patients, GD patients who had been treated for > 12 months (GD-T), autoimmune thyroiditis (AIT) patients, and healthy subjects (HS). The Immulite™ TSI and Elecsys Anti-TSHR assay were performed on all samples. According to their responsiveness to methimazole, the GD-UT patients were divided into rapid and slow responder groups, and their clinical characteristics were compared. A receiver operating characteristic (ROC) curve analysis of GD-UT patients showed that the optimal TSI cut-off value was 0.57 IU/L. Logistic regression revealed that age and initial FT4 and TSI levels in the middle-dose methimazole group were related to a rapid response, while the initial FT4 level, but not TSI, in the high-dose group was also associated with a rapid response. The clinical diagnostic performance of the Immulite™ TSI assay for diagnosing GD was comparable to that of the Elecsys Anti-TSHR assay. The initial FT4 and TSI levels can be used as predictors of the responsiveness to methimazole in patients with newly diagnosed GD. [ABSTRACT FROM AUTHOR]

• We evaluated the clinical performance of the TSI assay in the diagnose of GD in Chinese population. • The combined use of TSI and TRAb assay has been evaluated. • We compared the cases presenting with discordant TSI and TRAb results. We evaluated the use of thyroid stimulating immunoglobulin (TSI) assay to optimize the detection strategy for Graves' disease. Five hundred and forty-four well characterized serum samples from the Clinical Laboratory of Shanghai Tongren Hospital were collected from August 2019 to April 2020. The serum samples were obtained from 52 untreated GD patients, 155 treated GD patients, 83 patients with Hashimoto's thyroiditis, 70 patients with thyroid nodules, 83 patients with thyroid cancer, and 101 healthy subjects. All samples were evaluated by both TSI assay and TSH receptor autoantibodies (TRAb) assay. Moreover, 23 patients without a distinct thyroid disease diagnosis at the first visit were monitored for 6 months to make a final diagnosis. The clinical sensitivity of the TSI and TRAb assays was 98.10% and 94.20% respectively, while the clinical specificity was 92.30% and 96.70% respectively. ROC plot analysis based on sera of UT-GD (newly diagnosed GD patients) revealed an area under the curve (AUC) of 0.974 for the TSI assay. The best cutoff value was 0.58 IU/l (98.0% of sensitivity, 92.8% of specificity). The AUC for the TRAb assay was 0.961. Furthermore, combining TSI and TRAb results, the area under the curve was 0.981. In a pilot study of 23 patients with an uncertain initial diagnosis, the follow-up results showed the clinical diagnosis of 22 out of 23 cases were resolved in agreement with the results obtained by the TSI assay, and one case matched the result obtained by TRAb assay. The TSI assay presents very promising analytical characteristics and could be adopted in clinical practice to improve GD diagnosis. The TSI assay might be better than TRAb assay in initial differential diagnosis of GD from other thyroid diseases. [ABSTRACT FROM AUTHOR]

Despite the relation between autoimmune diseases and increased atherosclerotic risk is established, the influence of autoimmune disorders on in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) is only partly known. ISR is an aberrant reparative process mainly characterized by an increased number of vascular smooth muscle cells and excessive deposition of extracellular proteoglycans and type III collagen. Chronic inflammation, always present in autoimmune diseases, modulates the endothelial response to PCI. Aim of this review is to resume the current evidence on the association between ISR and autoimmune diseases, focusing on pathogenic mechanisms and therapeutic targets. We conducted a comprehensive review of the literature on the relationship between ISR and insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid-antibodies syndrome (APS), inflammatory bowel diseases (IBD), and Hashimoto's thyroiditis (HT). Patients affected with IDDM, RA, SLE, APS, IBD and HT proved to face higher rates of ISR compared to the general population. The endothelial dysfunction seems the principal common pathogenic pathway for ISR and is attributed to both the immune system disorder and the systemic inflammation. Some evidence suggested that methotrexate and anti-tumor necrosis factor treatments can be effective in reducing ISR, while antibodies against vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 showed to reduce neointimal hyperplasia in animal models. Autoimmune diseases are a risk factor for ISR. The study of the potential cardiovascular benefits of the current therapies, mainly anti-inflammatory drugs, and the pursuit of innovative treatments appear of paramount interest. [Display omitted] • Patients with autoimmune diseases are more prone to develop in-stent restenosis. • Insulin stimulates vascular smooth muscle cells after coronary revascularization. • Systemic lupus erythematosus is associated with more repeated revascularizations. • Antibodies against adhesion molecules reduce neointimal proliferation. • Endothelial dysfunction seems the final pathway of autoimmune induced restenosis. [ABSTRACT FROM AUTHOR]

RNA demethylase AlkB homolog 5 (ALKBH5) gene is pivotal in N6-methyladenosine (m6A) modification. Therefore, this study aimed to explore the potential relationship between polymorphisms of ALKBH5 gene and the development of autoimmune thyroid disease (AITD). A case-control study of 979 AITD patients, including 620 Graves' disease (GD) and 359 Hashimoto's thyroiditis (HT), and 732 normal controls of the Chinese Han population was performed using high-throughput sequencing (HiSeq) genotyping method for detecting 5 variants in ALKBH5 gene (rs12936694, rs2124370, rs4925144, rs8068517, and rs9913266). In addition, the associations between ALKBH5 single nucleotide polymorphisms (SNPs) and clinical phenotypes of AITD were investigated. Compared to normal controls, rs9913266 displayed significant differences in allele and genotype distributions in AITD and GD. rs12936694 also showed significantly different frequencies of alleles in AITD and GD. The link of these 2 loci polymorprhisms to AITD and GD also existed after adjusting for age and gender. When stratified by sex, the minor allele of rs9913266 was associated with the risk of female AITD and HT development before and after adjusting for age and gender. There was a significant association between rs8068517 locus and GD in females after adjusting for the confounders. Finally, we observed significant correlations of haplotypes CGACA and CAGCG to the susceptibility of AITD and GD. Our results provided evidence of association of polymorphisms in ALKBH5 gene with AITD, GD, and HT patients, and hence ALKBH5 might be the candidate gene for susceptibility to AITD. [ABSTRACT FROM AUTHOR]

• Auto-oxidized oxysterols are implicated in oxidative stress and atherosclerosis. • Auto-oxidized oxysterols are increased in subclinical-hypothyroidism. • Restoring euthyroidism improves levels of auto-oxidized oxysterols. • Treatment of subclinical hypothyroidism may decelerate the atherosclerotic process. Auto-oxidized oxysterols are implicated in the pathogenesis of various chronic diseases. Their concentrations are indicators of oxidative stress in vivo and associated with atherosclerosis. Subclinical hypothyroidism is related with cardiac diseases and oxidative stress, but the exact mechanisms underlying these associations are not clear yet. To investigate the auto-oxidized oxysterols, 7-ketocholesterol (7-KC) and cholestane-3β,5α,6β-triol (chol-triol), in patients with subclinical hypothyroidism, as well as to evaluate the impact of restoring euthyroidism on oxysterol concentrations. In this prospective observational study, 64 patients with newly diagnosed autoimmune thyroiditis (41 with subclinical hypothyroidism and 23 euthyroidism), and 45 healthy controls were enrolled. Age, gender, and body mass index were matched among patient groups and healthy controls. Anthropometric measurements were obtained and fasting plasma 7-ketocholesterol and cholestane-3β,5α,6β-triol concentrations were measured by using liquid chromatography coupled with tandem mass spectrometry. Levothyroxine was then administered to all patients with subclinical-hypothyroidism. After three months, measurements of the oxysterols and serum cholesterols from the patients who have become euthyroid were repeated. Concentrations of 7-ketocholesterol and cholestane-3β,5α,6β-triol were significantly higher in patients with subclinical-hypothyroidism when compared to both euthyroid patients and healthy controls (p < 0.001 for both oxysterols). After restoration of euthyroidism, concentrations of 7-ketocholesterol and cholestane-3β,5α,6β-triol decreased significantly and reached similar concentrations observed in healthy controls (p < 0.001 for both oxysterols). Auto-oxidized oxysterol species are higher in patients with mild thyroid dysfunction, and supported the rationale for treating subclinical-hypothyroidism. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis (HT) is the most frequent autoimmune disorder. Growing work points to the involvement of aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, in the regulation of immune homeostasis. However, the roles of AhR and its ligands in HT remains unclear. In this study, we leveraged public human database analyses to postulate that the AhR expression was predominantly in thyroid follicular cells, correlating significantly with the thyroid infiltration levels of multiple immune cells in HT patients. Using a thyroglobulin-induced HT mouse model and in vitro thyroid follicular epithelial cell cultures, we found a significant downregulation of AhR expression in thyrocytes both in vivo and in vitro. Conversely, activating AhR by FICZ, a natural AhR ligand, mitigated inflammation and apoptosis in thyrocytes in vitro and conferred protection against HT in mice. RNA sequencing (RNA-seq) of thyroid tissues indicated that AhR activation moderated HT-associated immune or inflammatory signatures. Further, immunoinfiltration analysis indicated that AhR activation regulated immune cell infiltration in the thyroid of HT mice, such as suppressing cytotoxic CD8+ T cell infiltration and promoting anti-inflammatory M2 macrophage polarization. Concomitantly, the expression levels of interleukin-2 (IL-2), a lymphokine that downregulates immune responses, were typically decreased in HT but restored upon AhR activation. In silico validation substantiated the binding interaction between AhR and IL-2. In conclusion, targeting the AhR with FICZ regulates IL-2 and immune infiltration to alleviate experimental HT, shedding new light on the therapeutic intervention of this prevalent disease. [Display omitted] [ABSTRACT FROM AUTHOR]

American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) being most widely applied in clinical practice, there is an overlap in US imaging manifestations between benign and malignant thyroid nodules. To analyze the imaging and histological characteristics of pathological benign thyroid nodules categorized as American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) 4 or 5, and to explore the correlation between the suspicious sonographic signs resulting in the misdiagnoses and the histopathological features. Overall, 227 benign thyroid nodules (215 patients) in ACR TI-RADS 4 or 5 sampled through surgical excision were analyzed between December 2020 and August 2022. We retrospectively reread the ultrasound (US) images of the pathological discordant cases, after which we performed a systematic analysis focusing on the histopathological characteristics of thyroid lesions and recorded the findings. Qualitative US features and pathological significance of the thyroid nodules were analyzed using the chi-square and Fisher's exact tests. The pathological type of 227 thyroid nodules (n = 103 in ACR TI-RADS 4 and n = 124 in ACR TI-RADS 5) was nodular goiter together with other histopathological features, namely, fibrosis (n = 103, 45.4 %), calcification (n = 70, 30.8 %), adenomatous hyperplasia (n = 31, 13.7 %), follicular epithelial hyperplasia (n = 23, 10.1 %), Hashimoto's thyroiditis (n = 18, 7.9 %), and cystic degeneration (n = 16, 7.1 %). Fibrosis was the most common histopathological feature in both ACR TI-RADS 4 (n = 42, 40.8 %) and 5 (n = 61, 49.2 %) categories of benign thyroid nodules. Thyroid nodules with fibrosis demonstrated sonographic features of "taller than wide" (p < 0.05), while lesions with follicular epithelial hyperplasia were likely to be detected with irregular and/or lobulated margins and very hypoechoic on US (p < 0.05 for both). Benign thyroid nodules with histopathological findings such as fibrosis are associated with suspicious US features, which may give inappropriately higher TIRADS stratification. [ABSTRACT FROM AUTHOR]

Polycystic Ovary Syndrome (PCOS) and Autoimmune Thyroiditis (AIT) are two prevalent endocrine disorders affecting women, often coexisting within the same patient population. This meta-analysis aims to systematically assess and synthesize the existing body of literature to elucidate the intricate relationship between PCOS and AIT. A systematic literature search for relevant observational studies was conducted in electronic databases such as Web of Science, Google Scholar, PubMed, Cochrane, and Scopus until March 2023. All Statistical analyses were performed using CMA Software v3.7 in a random-effects network meta-analysis. In addition, sensitivity and meta-regression analyses were conducted to identify sources of Heterogeneity based on related risk factors. Our meta-analysis included eighteen studies with 3657 participants, which revealed significant differences between PCOS patients and control groups. In particular, a considerable association was detected between PCOS and the presence of AIT (OR = 2.38; 95% CI: 1.63–3.49; P< 0.001) and elevated levels of TSH (SMD = 0.24; 95% CI: 0.06–0.42; P= 0.01), anti-TPO (SMD = 0.36; 95% CI: 0.19–0.53; P< 0.001), anti-TG (SMD = 1.24; 95% CI: 0.37–2.10; P< 0.001), and other positive serum antibodies compared to the control groups. The findings from this meta-analysis may contribute to enhanced diagnostic strategies like complete thyroid function tests, more targeted interventions, and improved patient care for individuals presenting with both PCOS and AIT. Additionally, identifying commonalities between these conditions may pave the way for future research directions, guiding the development of novel therapeutic approaches that address the interconnected nature of PCOS and AIT. [ABSTRACT FROM AUTHOR]

Iodine excess (IE) intake leads to lymphocyte dysfunction and contributes to autoimmune thyroiditis (AIT). Abnormal thyroid function is associated with adverse cardiovascular events, endothelial dysfunction is often an early pathophysiological feature in most cardiovascular disease. However, the relationship between iodine and the cardiovascular system is currently unclear. Therefore, the aim of this study was to investigate the effects of IE on endothelial function in mouse model. A total of 24 NOD.H-2h4 mice were randomly divided into different groups. A sodium iodide (NaI) group supplied with 0.05% NaI water for 8 weeks. Serum levels of tumor necrosis factors α (TNFα), interleukin-6 (IL-6) and C-reactive Protein (CRP), as well as endothelin-1 (ET-1), von Willebrand factor (VWF) and thrombomodulin (THBD) were detected by Elisa. In addition, the mRNA and protein expression of these genes were measured by RT-PCR and Western blotting. Here, we found the urinary iodine concentration (UIC) was higher in the NaI group compared to the control group. Serum levels of ET-1, VWF, and THBD were also significantly lower in the NaI group, however, CRP serum levels are significantly increased. In aorta, the mRNA and protein expression of ET-1, VWF, THBD were downregulated, however, the expression of IL-6, CRP and TNFα mRNA and protein were upregulated in the NaI group. A correlation analysis showed negative correlation between UIC with ET-1, VWF, and THBD, similarly, negative correlation between CRP with THBD was observed. In addition, positive correlations between UIC with CRP. Collectively, in the NOD.H-2h4 mice, IE supplementation had a suppressive effect on endothelial function, and this inhibition maybe due to the increase expression of inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Autoimmune Thyroiditis (AIT) is a common refractory autoimmune disease of the endocrine system that may eventually lead to complete loss of thyroid function, with subsequent severe effects on the metabolism. Because of the deficiency in current clinical management of AIT, the need for alternative therapies is highlighted. With its multi-component and multi-target characteristics, Chinese medicine has good potential as an alternative therapy for AIT. The aim of this study was to systematically summarize the clinical efficacy and safety evaluation of TCM and its active ingredients in the treatment and regulation of AIT. Additionally, we provide an in-depth discussion of the relevant mechanisms and molecular targets to understand the protective effects of traditional Chinese medicine on AIT and explore new ideas for clinical treatment. The literature related to "Hashimoto", "autoimmune thyroiditis", "traditional Chinese medicine," and "Chinese herbal medicine" was systematically summarized and reviewed from Web of Science Core Collection, PubMed, CNKI, and other databases. Domestic and international literature were analyzed, compared, and reviewed. An increasing number of studies have demonstrated that herbal medicines can intervene in immunomodulation, with pharmacological effects such as antibody lowering, anti-inflammatory, anti-apoptotic thyroid follicular cells, regulation of intestinal flora, and regulation of estrogen and progesterone levels. The signaling pathways and molecular targets of the immunomodulatory effects of Chinese herbal medicine for AIT may include Fas/FasL, Caspase, BCL-2, and TLRs/MyD88/NF-κB et al. The use of Chinese herbs in the treatment and management of AIT is clinically experienced, satisfactory, and safe. Future studies may evaluate the influence of herbal medicines on the occurrence and development of AIT by modulating the interaction between immune factors and conventional signaling pathways. [Display omitted] • Traditional Chinese medicine offers potential as alternative therapy for autoimmune thyroiditis (AIT). • Herbal medicines have demonstrated immunomodulatory effects through various signaling pathways and molecular targets. • Clinical efficacy of traditional Chinese medicine in treating AIT is satisfactory and safe. [ABSTRACT FROM AUTHOR]

Conventional treatments for Hashimoto's thyroiditis (HT) are limited. Herbal medicines (HM) are considered a potential intervention for the treatment of HT. This study aimed to investigate the efficacy and safety of HM for HT. A Bayesian network meta-analysis was conducted for patients with HT in randomized controlled trials identified in PubMed, Cochrane Library, Web of Science, EMBASE, Chinese Clinical Trial Registry (Chi CTR), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (the VIP), China Chinese Biomedical Database (CBM), and Wanfang Database were searched from their inception to Oct 1, 2022. Outcomes included the primary outcome (TPOAb), secondary outcomes (TSH, TGAb, FT3, FT4, and traditional Chinese medicine symptom scores), and adverse events. This study was registered in PROSPERO (CRD42022363640). Sixteen trials were reviewed and 16 HM formulae were compared. Compared with non-drug therapy (NDT), all therapies, except for Tiaoqi-Qingjie Therapy, reduced the primary outcome of TPOAb with different levels of effectiveness, ranging from 0.01 (95%CI 0.00, 0.02) to 0.92 (95%CI 0.56, 1.53). Ranking probability analysis indicated that Yiqi Huayu Recipe, Liqi Xiaoying decoction, and Shugan Sanjie therapy reduced thyroid antibody levels the most, including TPOAb (100.0%, 90.9%, and 90.3%, respectively) and TGAb (98.3%, 94.4%, and 87.3%, respectively). All HMs displayed a significant effect on the TCM Symptom score and possibly benefitted the treatment of HT, ranging from 6.62 (95% CI 2.06, 21.24) to 94.50 (95% CI 15.97, 559.14). No serious adverse events were reported. Herbal medicines may be effective in the treatment of HT, especially in reducing thyroid antibody levels and improving clinical symptoms without affecting thyroid function. However, these results should be considered preliminary and further verified using high-quality evidence. [Display omitted] • There is no appropriate treatment for patients with only elevated antibodies and/or hyperthyroidism like symptoms. • Herbal medicines have favorable risk-benefit profiles treatments of HT to reduce thyroid antibodies. • Herbal medicine can play an important role in improving HT symptoms. [ABSTRACT FROM AUTHOR]

Childhood Mixed Connective Tissue Disease (cMCTD) is the rarest pediatric connective tissue disease that includes features of systemic lupus erythematosus, polymyositis/dermatomyositis, juvenile idiopathic arthritis, and systemic sclerosis, identified by Sharp in 1972 and whose diagnosis remains challenging. This systematic review aims to identify clinical features at the onset of cMCTD and manifestations not currently included into the available diagnostic criteria. A systematic literature review was performed in accordance with PRISMA guidelines 2020 using bibliographic databases: MEDLINE via PubMed and EMBASE. Eligibility criteria: patients diagnosed with MCTD with onset before 18 years. Studies included: registries, retrospective and prospective cohort studies, case series and reports with analysis of data on signs and symptoms of presentation. 39 articles were included (215 subjects, 82.5% female), mean age of 141 months (± 41 months DS, range 2.5–204). The most used criteria for the diagnosis of MCTD were the Kasukawa criteria (54.5%). The clinical manifestations described at onset were Raynaud's phenomenon (69.7%), arthritis (60.9%), muscular involvement (53.5%), dermatological signs (39.5%), swollen fingers or hands (29.3%), arthralgias (25.6%), fever (22.3%), lung involvement (14.4%), sclerodactily (13.5%), lymphadenopathy (10.7%) serositis (10.2%), esophageal involvement (6.9%), nervous system involvement (6.9%), xeroftalmia (3.7%), xerostomia (3.7%), hepatosplenomegaly (2.8%), cardiac involvement (2.8%), hepatitis (2.3%), parotiditis (2.3%), Hashimoto's thyroiditis (0.9%), ocular involvement (0.9%). The data from this systematic review suggest great heterogeneity of the clinical presentation of cMCTD for which there are no validated diagnostic criteria that may suggest a new diagnostic approach to allow earlier or more accurate diagnosis in the future. • What is already known on this topic: cMCTD is a rare disease and diagnosis is difficult as the literature lacks the characteristics of the disease at onset. • What this study adds: this study suggests a great heterogeneity of the clinical presentation of cMCTD, with features not included in the diagnostic criteria. • How this study might affect research, practice or policy – this study could suggest a new diagnostic approach or help clinicians make a more accurate or earlier diagnosis. [ABSTRACT FROM AUTHOR]

Further clinical trials are proposed for the 5–15% of hypothyroid patients who are dissatisfied with thyroxine (T4) monotherapy. Those responding to combination therapy [T4 plus triiodothyronine (T3)] will show suggestive biochemistry and abnormal reflexes. Those with Hashimoto's disease and very high anti-thyroid peroxidase (anti-TPO) thyroid antibody levels may benefit from total thyroidectomy. The remainder have negative clinical and laboratory findings and require supportive management. [ABSTRACT FROM AUTHOR]

The effects of amino acid variants encoded by human leukocyte antigen (HLA) class II on the development of Graves' disease (GD) and Hashimoto's thyroiditis (HT) have not been fully elucidated. We investigated the HLA-DRB1 genes of 243 GD patients and 82 HT patients in the Japanese population and compared the frequencies of HLA-DRB1 alleles and HLA-DRB1 amino acid variants between these patients and the Japanese populations previously reported by another institution. The frequencies of HLA-DRB1*04:05 and -DRB1*14:03 alleles were significantly higher and those of HLA-DRB1*01:01 and -DRB1*15:02 alleles were lower in GD patients than in controls. The frequencies of HLA-DRB1*08:03 and -DRB1*09:01 alleles were significantly higher and that of the HLA-DRB1*13:02 allele was lower in HT patients than in controls. A blind association analysis with all amino acid positions identified DRß9 and DRß31 for GD and DRß9, DRß13, and DRß21 for HT. The frequency of Glu-9 was significantly higher and that of Cys-9 was lower in GD patients than in controls. The frequencies of Lys-9 and Phe-13 were significantly higher in HT patients than in controls. DRß9 and DRß13 could be critical amino acid positions in the development of GD and HT. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory polyarthropathy that affects many synovial joints favoring the hands, knees, and vertebral articulations. Joint laxity manifests as subaxial instability, atlantoaxial instability, and cranial settling (CS). A 70-year-old woman with past medical history of RA, Hashimoto's thyroiditis, osteoporosis, history of C1-2 fusion for instability 15 years prior, with subsequent revision cervicothoracic fusion for degeneration, and trauma 2 years prior presents with new onset headache, nausea, and vomiting of 36-hour duration. Neurologic examination was only notable for mild right dysmetria. Workup revealed acute hemorrhage in the posterior fossa with migration of the right rod implant and screw tulip, as a result of CS. The patient underwent occipital-cervical fusion with removal of the migratory hardware. Intracranial rod migration and hemorrhage secondary to CS is a rare complication that must be brought to the attention of surgeons operating on patients with RA. [ABSTRACT FROM AUTHOR]

To evaluate diagnostic performance of PACS-based quantitative gray-scale ultrasound as an objective method in evaluation of pediatric thyroiditis. Quantitative measurements of the echo-intensity level of the thyroid were obtained from ultrasound images, retrospectively using a PACS-based tool in 37 children with the tissue-proven diagnosis. Thyroid/muscle ratio was calculated by dividing the mean echo intensity of thyroid by that of adjacent strap muscle. Heterogeneity index (HI) was calculated by dividing thyroid standard deviation (SD) by thyroid mean values. For qualitative evaluation, two radiologists independently reviewed ultrasounds twice for the presence of thyroiditis. A consensus session was performed for patients for whom there was disagreement. Intra- and inter-observer reliability were assessed. Thyroid/muscle ratio and HI were correlated with final pathology. Lymphocytic thyroiditis was found by histopathology in 19/37 (51%). No significant difference between thyroiditis and normal thyroid groups was found for either thyroid/muscle ratio (1.51 and 1.62, respectively, p =.82) or HI (0.23 and.23, respectively, p =.37). A larger proportion of patients for whom the consensus review indicated thyroiditis were confirmed by histopathology than would be expected by chance alone (12/19 (63%), p =.03). There was fair inter-observer agreement (κ with 95% confidence intervals of 0.36 (0.14–0.57), p =.004) and slight intra-observer agreement for each radiologist (κ with 95% confidence intervals of 0.13 (0.17–0.43), p =.39 and 0.17 (0.15–0.49), p =.31). Quantitative gray-scale echo intensity analysis of US was not sufficient to diagnose thyroiditis in a pediatric population. Consensus qualitative analysis of ultrasound was more consistent with pathological diagnosis. • Quantitative grayscale ultrasound was not sufficient to accurately distinguish thyroiditis from normal thyroid tissue in pediatrics. • Qualitative consensus visual evaluation by two radiologists showed a significant correlation in distinguishing thyroiditis in pediatrics. • Double reading may be beneficial for accurate diagnosis of thyroiditis in children. [ABSTRACT FROM AUTHOR]