Search Results (118)

Down Syndrome (DS) is the most common chromosomal abnormality characterized by neurodevelopmental impairment. Apart from maternal age, its risk factors remain poorly understood. This prospective case-control study aimed to evaluate the role of maternal anti-zona pellucida (ZP) antibodies (Ab) and anti-thyroid-Ab in predicting DS. Correlations of anti-ZP-Ab and anti-thyroid-Ab with maternal age were also assessed. Anti-ZP-Ab were measured after childbirth using ELISA. Anti-thyroid peroxidase (aTPO) and anti-thyroglobulin (aTgII) antibodies were also analysed with the Allelica IM platform. Statistical analyses included receiver operating characteristic curve assessment, expressed as area under the curve (AUC) and linear regression modeling. Between September 2020 and October 2022, 58 women were enrolled. Anti-ZP-Ab levels were significantly higher in women with DS pregnancy with an odds ratio adjusted for maternal age of 71.52 (95% CI: 7.05–725.18) and an excellent predictive performance (AUC = 0.94; 95% CI: 0.88–1.00). For optical density levels > 1, the accuracy was 89.7% (95% CI: 78.2–100.0). No statistically significant differences were observed for aTPO and aTgII. Neither Anti-ZP-Ab nor anti-thyroid antibodies increased with age. These findings suggest that Anti-ZP-Ab are strongly associated with DS risk, suggesting a potential age-independent autoimmune contribution to trisomy 21. Their evaluation may support preconception counseling, especially for women aged > 35 years. Future studies could clarify causality and define the role of maternal autoimmunity in DS etiology. Full article

Background and clinical significance: Idiopathic hypertrophic pachymeningitis (IHPM) is a rare inflammatory disorder characterized by diffuse or focal dural thickening and heterogeneous presentations. We report a corticosteroid-responsive IHPM with elevated anti-thyroglobulin (anti-Tg) antibodies despite oncologic control after thyroidectomy. This case suggests that systematic assessment for autoimmunity should be a standard component of the IHPM work-up. Case presentation: A 77-year-old woman presented with recurrent vertigo, imbalance, and headaches. Brain MRI showed diffuse pachymeningeal thickening with mild heterogeneous enhancement, radiologically stable over >2 years. Extensive evaluation excluded infectious, neoplastic (including paraneoplastic), cerebrospinal fluid hypotension and systemic autoimmune causes; findings did not support IgG4-related disease. Thyroid work-up revealed hypothyroidism with multinodular goiter; total thyroidectomy was performed, and there was no indication for adjuvant radioiodine therapy. Despite oncologic control, anti-Tg antibodies remained markedly elevated, while anti-thyroid peroxidase antibodies (anti-TPO) declined. Symptoms repeatedly improved with oral methylprednisolone and recurred on taper; adverse effects were mild and manageable. The patient remains under clinical and oncologic surveillance with symptom-guided steroid re-challenge. Conclusions: IHPM may exhibit a dissociation between clinical response and radiologic course. Persistently elevated anti-Tg after thyroidectomy can coexist with IHPM and may signal ongoing autoimmunity rather than active cancer. Full article

Cervical cancer (CC) can be prevented through continuous screening and the timely detection of cervical intraepithelial neoplasia (CIN) using immunohistochemistry techniques to identify biomarker expressions. In a previous study, we proposed nuclear REST loss as a biomarker in precancerous lesions and CC; however, no validated antibodies are available for detecting REST in cytology or cervical tissues. Although we have developed an IgM-type anti-REST monoclonal antibody capable of detecting REST in liquid-based cytology cells, it was not useful for the detection of REST in cervical tissues by immunohistochemistry. The main objective of this study is to generate single-chain variable fragments (scFvs) for the clinical evaluation of REST in cervical tissues from women with CIN and CC. Using RNA from an IgM-producing hybridoma anti-REST, we conducted RT-PCR and PCR to obtain the coding sequences for the variable regions of the heavy and light chains. These sequences were joined with a linker to create a single-chain antibody. The scFv was then cloned into the pSyn1 vector, expressed in E. coli TG1, and purified through chromatography. Subsequently, it was characterized using immunological methods to assess its biological activity and employed to evaluate REST expression in cytological samples and cervical tissues. The anti-REST scFv represents an innovative detection tool that retains the antigen recognition of the parental IgM while overcoming its size limitation, enabling tissue penetration and detection of REST in cervical samples. Its application facilitates the identification of REST in cervical samples, reinforcing REST’s potential as a diagnostic biomarker for CC and CIN. Full article

In contemporary medical practice, human thyroglobulin (Tg) stands out as the primary serum biomarker for detecting recurrence or persistence (presence of residual tumor) of differentiated thyroid carcinoma (DTC) in patients post-thyroidectomy. Immunoassays (IMAs) and radioimmunoassays (RIAs) have been implemented in clinical settings to gauge Tg levels. However, these methods can be unreliable because anti-thyroglobulin antibodies (Tg-Abs) and heterophile antibodies (HAs) interfere with assay binding, leading to either under- or overestimation of true Tg concentrations. Liquid chromatography tandem mass spectrometry (LC-MS/MS) has emerged as a distinctive alternative tool for Tg measurements. Despite its potential, the effectiveness of LC-MS/MS is under ongoing investigation. This review aims to provide a clear overview of existing follow-up procedures for Tg quantification and evaluate the potential of mass spectrometry (MS) in Tg analysis. The distinctive contribution of this review is the introduction of an emerging approach combining dried blood spots (DBSs) with LC-MS/MS for Tg measurement, emphasizing their translational potential for clinical follow-up of DTC patients. Full article

Introduction: There is limited data in the literature on the effect of prostaglandins (PG) and thromboxanes (TX) on the development and severity of Hashimoto’s Thyroiditis (HT). This article aimed to analyze the association between blood count and the cyclooxygenase (COX) pathway in 39 women with HT. Methods: Biochemical analysis of PGE2 and TXB2 was performed using liquid chromatography (HPLC). Results: Morphological abnormalities were found in the women studied, particularly with regard to white blood cell parameters. An increase in thyroid-stimulating hormone (TSH) was associated with significantly higher levels of monocytes (p = 0.041). Correlations were also noted between the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) with TXB2 and PGE2. Furthermore, a very strong correlation was demonstrated for the first time between antibodies against tissue transglutaminase (anti-tTG) and antibodies against thyroglobulin (ATG) (r = 0.781; p = 0.007). Correlations between blood count and eicosanoids were also demonstrated. Conclusions: The results suggest the involvement of COX products in the pathogenesis of HT and hematopoiesis; therefore, this study may contribute not only to advancing knowledge, but also to developing new guidelines for diagnosing and treating autoimmune diseases. Full article

Introduction: Vitamin D is involved in numerous processes and is obtained both exogenously and endogenously. Its active form is 1,25-dihydroxycholecalciferol, which exerts its biological effects via the vitamin D receptor (VDR). The main factors influencing VDR density are polymorphisms of the VDR gene, which may affect, e.g., gene mRNA stability and also VDR gene expression. There are four main polymorphic sites within the gene, BsmI, ApaI, FokI and TaqI, and two polymorphisms related to the gene promoter: GATA and Cdx2. One of the functions of vitamin D is to modulate the immune system. It affects T lymphocytes, B lymphocytes and dendritic cells. Currently, vitamin D deficiency is a common global problem that is associated with an increased risk of autoimmune diseases, including Hashimoto’s thyroiditis. Numerous studies have demonstrated an association between low vitamin D levels and elevated thyroid-stimulating hormone (TSH) levels, and have also proven the existence of a negative correlation between vitamin D levels andanti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibody titers. Review objectives and a concise summary of the methodology: The review aims to analyze studies examining the relationship between specific VDR polymorphisms, vitamin D levels, and the development of various diseases, with a particular emphasis on Hashimoto’s thyroiditis. This review is based on original and review articles written in English published between March 2018–November 2024 searched primarily in the PubMed, and additionally in Google Scholar databases. A narrative review of the literature was conducted. Conclusions: The presence of specific VDR polymorphisms influences the effectiveness of vitamin D supplementation, but the role of supplementation in the prevention of autoimmune diseases has not been definitively confirmed. To date, studies have primarily involved relatively small groups of patients with significant population heterogeneity, with case–control investigations being the most common. Therefore, further research on larger, more homogeneous groups is recommended to achieve more standardized results. Additionally, the influence of epigenetic factors modulating VDR activity and its interactions with the environmental factors is also important. Full article

Background: Thyroid dysfunction, including non-thyroidal illness syndrome (NTIS), is commonly observed in critically ill patients and has been reported in COVID-19, particularly in those with severe disease. NTIS is defined by low free triiodothyronine (fT3) with normal or low thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels. Thyroid autoantibodies may also reflect immune system activation. The relationship between thyroid hormone alterations, autoimmunity, and clinical severity in COVID-19 remains incompletely understood. Methods: We conducted a retrospective study of 276 patients hospitalized with COVID-19, including 138 in the intensive care unit (ICU) and 138 in general wards. A control group of 110 hospitalized, non-infected patients was also analyzed. Serum concentrations of TSH, fT3, fT4 and reverse T3 (rT3) were measured. The presence of anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-Tg), and thyrotropin receptor antibodies (TRAb) was assessed. Results: NTIS was observed in 44.2% of ICU patients, 18.1% of non-ICU patients, and 1.8% of controls. The fT3/rT3 ratio was lowest in ICU patients (median 0.11 vs. 0.16 in non-ICU and 0.22 in controls). Thyroid autoantibodies were significantly more prevalent in COVID-19 patients than in controls, with anti-TPO antibodies being the most frequently detected. Their presence, even in patients without known thyroid disease, may reflect immune activation associated with SARS-CoV-2 infection. Conclusions: NTIS and thyroid autoimmunity are frequent in hospitalized COVID-19 patients and may reflect disease severity and immune activation. Our study highlights the prognostic relevance of routine thyroid testing, including the fT3/rT3 ratio and combined autoantibody positivity (notably the triple-positive pattern), by directly comparing ICU and non-ICU patients with a non-COVID control group. Full article

Background/Objectives: To establish reference intervals (RIs) and cut-off values for thyroid-related tests on the MAGLUMI X6 immunoassay analyzer (Snibe Diagnostic, Shenzhen, China) in an adult Croatian population. Methods: This study included 305 healthy individuals who underwent regular preventive medical checkup. The following tests were determined in serum: thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin (Tg), reverse triiodothyronine (revT3), total binding capacity of thyroglobulin (T-uptake), thyroglobulin antibodies (anti-Tg), anti-thyroid peroxidase antibodies (anti-TPO) and thyroid receptor antibodies (TRAb). TSH, TT3, TT4, FT3, FT4, Tg, revT3 and T-uptake results were used for calculating double-sided 95% RIs between the 2.5th and 97.5th percentiles. For anti-Tg, anti-TPO and TRAb, right-sided cut-offs that correspond to the 95th percentile were determined. Results: Reference intervals for TSH, TT4, FT3, FT4, Tg, T-uptake and revT3 did not differ by gender (p > 0.05) and were 0.77–5.04 mIU/L, 69.9–127.7 nmol/L, 3.84–6.20 pmol/L, 13.8–19.7 pmol/L, 1.8–51.2 µg/L, 0.9–1.2 TBI and 0.44–0.73 ng/mL, respectively. The RI for TT3 was different for males (1.49–2.53 nmol/L) and females (1.43–2.81 nmol/L), p = 0.021. A single cut-off for anti-TPO was established (<18 kIU/L). Differences in cut-offs for males and females were obtained for anti-Tg (<72 and <104 kIU/L, respectively) and TRAb (0.6 and 0.9 IU/L, respectively). Conclusions: This is the first study to determine RIs for thyroid function tests in Croatian adults on the Snibe analytical platform. The obtained results point out to the use of population- and immunoassay-specific RIs. For TT3, anti-Tg and TRAb gender-specific RIs should be considered. Full article

Polycystic ovary syndrome (PCOS) is a prevalent endocrinological condition among women of reproductive age, characterized by several well-known symptoms, including hyperandrogenism, anovulation, irregular menstrual cycles, and insulin resistance. In addition, women suffering from PCOS are also at an increased risk of developing several autoimmune diseases, including thyroid disorders, type 1 diabetes, and rheumatoid arthritis. Furthermore, an elevated prevalence of diverse autoantibodies is observed in women diagnosed with PCOS. These include antibodies specific to autoimmune diseases, e.g., anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG), and antinuclear antibodies (ANAs), as well as those that are non-specific, such as anti-malondialdehyde-modified human serum albumin (anti-HSA-MDA) or anti-α-crystallin. It appears that several mechanisms may be responsible for this phenomenon. PCOS has been observed to co-occur with autoimmune diseases, potentially attributable to shared genetic susceptibility or the presence of hormonal disorders resulting from autoimmune diseases. Moreover, PCOS is a chronic low-grade inflammatory disease that may contribute to immune dysfunction and subsequent overproduction of autoantibodies. A further intriguing aspect may be the yet-unknown role of autoantibodies in the pathogenesis of PCOS, considering PCOS as a disease with an autoimmune etiology. Full article

Polycystic ovary syndrome (PCOS) is a complex condition affecting women of reproductive age, characterized by menstrual irregularities, hyperandrogenism, polycystic ovarian morphology, and low-grade inflammation accompanied by oxidative stress and increased autoimmune risk, particularly Hashimoto’s thyroiditis. Many studies have examined thyroid autoantibodies—anti-thyroid peroxidase antibodies (anti-TPO) and anti-thyroglobulin antibodies (anti-TG)—in PCOS; however, observed differences in baseline thyroid-stimulating hormone (TSH) levels and body mass indices (BMIs) impede a direct interpretation of the results. This systematic review and meta-analysis aimed to summarize the available evidence on the prevalence and levels of anti-TPO and anti-TG in women with PCOS. We conducted a systematic search of PubMed, Scopus, and Embase, which yielded 40 eligible, observational studies including 6045 women with PCOS and 4527 controls. Subgroup analyses were conducted separately for TSH- and BMI-matched populations. Anti-TPO prevalence (odds ratio [OR] = 2.03; 95% confidence interval [CI]: 1.35–3.04; p = 0.0006) and levels (standardized mean difference [SMD] = 0.63; 95% CI: 0.37–0.88; p < 0.00001) were significantly higher in PCOS patients. Anti-TG prevalence (OR = 1.92; 95% CI: 1.23–3.01; p = 0.004) and levels (SMD = 0.41; 95% CI: 0.18–0.64; p = 0.0004) were also significantly elevated. In matched subgroups, prevalence differences were no longer significant, though anti-TPO levels remained significantly elevated and anti-TG levels were borderline significant in the TSH-matched subgroup of PCOS women. Although differences in thyroid autoantibody prevalence in women with PCOS appear to be driven by elevated TSH levels and BMIs, the persistently increased antibody levels in the majority of matched subgroups suggest that PCOS itself may contribute independently to heightened autoimmune activation. Full article

A large cohort of Romanian children suspected of celiac disease (CD) received comprehensive evaluation through this study regarding serological, genetic, and biochemical markers. This study investigated the relationships between anti-tissue transglutaminase (anti-tTG), anti-endomysium antibodies (EMAs), anti-gliadin deamidated (DGP) antibodies, and HLA genotyping. A strong association was observed between high anti-tTG IgA titers (>100 U/mL) and EMA IgA positivity, with a 95% concordance rate. Furthermore, anti-tTG IgA positive correlated with a significant prevalence of DGP antibodies, suggesting the complementary diagnostic role of DGP antibodies in equivocal cases. Genetic testing for HLA-DQ2/DQ8 alleles validated their association with celiac disease susceptibility, with 50% of the studied patients exhibiting these markers. The research reveals that vitamin D insufficiency affects a large number of children with anti-tTG antibodies, thus requiring both screening and supplementation practices. Furthermore, associations with other autoimmune conditions were explored, including thyroid and diabetes-related autoantibodies. This research demonstrates why CD diagnosis and management require a complete approach that combines serological tests with genetic evaluation and prompt intervention for related health conditions. Full article

Background/Objectives: Coeliac disease is an immune-mediated disorder of the gastrointestinal tract that may result in significant nutritional deficiencies. Effective management requires strict, lifelong adherence to a gluten-free diet. Both underdiagnosis and unnecessary dietary restrictions can adversely affect patients’ health and quality of life. To assess adherence to the current recommendations for the laboratory diagnosis of coeliac disease and promote evidence-based practices while reducing inter-laboratory variability, the Spanish Group on Autoimmunity of the Spanish Society of Immunology conducted a nationwide survey. Methods: A thirty-item survey was distributed to fifty autoimmune laboratories across Spain. Data were collected through a structured Excel-based questionnaire comprising multiple-choice items, which was distributed via email to the participating laboratories. It explored practices related to the diagnosis of coeliac disease in the general population and among at-risk groups as well as approaches to patient follow-up and demand management. Results: Thirty-five laboratories completed the electronic questionnaire. For the serological screening of coeliac disease, all the respondents reported using IgA anti-tissue transglutaminase (tTG-IgA) antibody testing together with total IgA measurement to assess IgA competence. However, consistent use of anti-endomysial antibody testing and HLA genotyping and adherence to pre-analytical recommendations for accurate interpretation of results were not uniform across centres. Conclusions: At the time these data were collected (the third trimester of 2021), the 2020 ESPGHAN guidelines for the diagnosis of coeliac disease in the paediatric population had not yet been fully implemented in most of the laboratories surveyed. For diagnosing adults, most laboratories adhered to local and European guidelines. Full article

Background: A novel and highly effective strategy for tumor immunotherapy involves enhancing host immune responses against tumors through the blockade of checkpoint molecules. The most common toxicities associated with checkpoint blockade therapies include autoimmune damage to various organs. Purpose: This study aims to investigate hematological markers derived from complete blood counts (CBCs)—including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (dNLR), white blood cell-to-hemoglobin ratio (WHR), neutrophils, lymphocytes, platelets, hemoglobin, red blood cell (RBC) count, neutrophil-to-RBC ratio (NRR), and neutrophil-to-hemoglobin ratio (NHR)—as potential prognostic biomarkers for the early identification of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 immune checkpoint inhibitors. Materials and Methods: A prospective observational study was conducted on 44 patients with stage III-IV solid tumors treated with immune checkpoint (PD-1 or PD-1/CTLA-4) inhibitors. Thyroid function tests and CBC-derived biomarkers were collected at baseline, before immunotherapy. In the immunotherapy cohort, 15 of the 44 patients developed immune-related hypothyroidism, defined as overt autoimmune thyroiditis (TSH > 4.0, FT4 < 12, and anti-TPO antibodies > 30 IU/mL and/or anti-TG antibodies > 95 IU/mL) (Group 1). In comparison, 29 patients maintained normal thyroid function (Group 2). The control group comprised 14 age- and sex-matched healthy volunteers (Group 3). Statistical analyses were performed using analysis of variance (ANOVA) to compare blood parameters among the three groups (Group 1, Group 2, and Group 3) before treatment, with statistical significance set at a p-value < 0.05. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic power of the potential prognostic biomarkers areas. The area under the curve (AUC), sensitivity, and specificity were calculated for the 44 immunotherapy patients. Results: The PLR was significantly higher (262.25 ± 162.95), while WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes were lower (2.07 ± 0.66, 0.54 ± 0.19, 0.96 ± 0.28, 0.36 ± 0.14, 6.36 ± 2.07, 4.29 ± 1.55, and 1.23 ± 0.41, respectively) at baseline in Group 1 in comparison to Group 2. ROC curve analysis revealed that the areas under the curve (AUC) for WBCs, neutrophils, lymphocytes, WBCs-neutrophils, the PLR, the WHR, the NRR, and the NHR were 0.9, 0.87, 0.83, 0.85, 0.84, 0.92, 0.89, and 0.87, respectively. These values exceeded the threshold, indicating the high prognostic potential of each marker. Conclusions: Lower baseline levels of WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes, along with a higher PLR, were associated with an increased risk of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 inhibitors. These CBC-derived biomarkers represent simple, accessible, and potentially useful tools for predicting hypothyroidism in cancer patients undergoing immunotherapy. Further studies in bigger cohorts are needed to validate our findings. Full article

Background/Objectives: Hashimoto’s thyroiditis (HT) is the most common cause of hypothyroidism during childhood and adolescence. Children and adolescents with HT have an increased susceptibility to the development of thyroid nodules and thyroid cancer. Among the genetic causes of thyroid cancer, the 677C>T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene is also reported. This study investigated for the first time the association between the 677C>T polymorphism (rs1801133) of the MTHFR gene and HT in children and adolescents. Methods: This case–control study included 130 children and adolescents with HT and 130 healthy controls. The 677C>T polymorphism of the MTHFR gene was studied in all participants with Restriction Fragment Length Polymorphism (RFLP) methodology for genetic variance analysis. Results: Children and adolescents with HT presented approximately 2.5 times more frequently the T allele sequences (CT and TT variants) and the T alleles in total for the 677C>T polymorphism of the MTHFR gene compared to the healthy population (OR: 2.56, CI: 1.53–4.21 and OR: 2.57, CI: 1.59–4.16, respectively). Children and adolescents with HT and T allele sequences (CT and TT variants) exhibited abnormal thyroglobulin antibodies (anti-TG) two times more frequently compared to those with the wild-type (CC) sequence in the same population (OR: 2.13, CI: 1.04–4.389). Conclusions: Children and adolescents with HT showed an increased frequency of T allele sequences (CT and TT variants) and total T alleles of the 677C>T polymorphism of the MTHFR gene compared to the healthy population. Full article

Receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast formation and bone resorption, in osteolytic conditions such as osteoporosis and bone metastases. However, its role in metastasis progression remains incompletely understood. Herein, we examined whether the overexpression of human RANKL in transgenic mice (TgRANKL) affects their susceptibility to breast cancer bone metastasis compared to their wild-type (WT) littermates. Bone metastasis was induced by injecting EO771 mouse mammary adenocarcinoma cells into the caudal artery of syngeneic WT and TgRANKL mice. RANKL overexpression led to an earlier onset and increased burden of bone metastasis in EO771-bearing TgRANKL mice compared to WT mice. It also exacerbated the bone destruction caused by metastasis-associated osteolysis. The prophylactic inhibition of RANKL activity with denosumab, a monoclonal antibody targeting human RANKL, prevented osteolysis and significantly reduced the incidence and progression of bone metastases in TgRANKL mice. However, the therapeutic denosumab treatment had no effect on metastasis incidence or tumor burden, although it alleviated osteolysis. The treatment with zoledronic acid, an anti-resorptive agent inhibiting osteoclast activity, yielded results similar to those of denosumab. These findings emphasize the significance of initiating early treatment with anti-resorptive agents such as denosumab or zoledronic acid to reduce the risk of bone metastasis in patients at high risk. Full article