Background: Hashimoto’s thyroiditis (HT) is a common autoimmune thyroid disorder characterized by elevated anti-thyroid peroxidase (A-TPO) antibodies. HT frequently coexists with other autoimmune conditions, which are marked by organ-specific and non-organ-specific autoantibodies, reflecting a deregulated immune response. However, the burden and clinical significance of these circulating autoantibodies in adult patients with HT remains unclear. Methods: A cross-sectional study was conducted at the University Hospital “R. Dulbecco” in Catanzaro, Italy, from November 2023 to May 2024, involving 200 euthyroid adults. The study population comprised 100 A-TPO-positive HT patients and 100 A-TPO-negative controls, matched for age and sex. Laboratory assessments included thyroid function tests and detection of autoantibodies [e.g., antinuclear antibodies (ANA), anti-parietal cell antibodies (APCA), and anti-neutrophil cytoplasmic antibodies (ANCA)]. Cytokine profiles were also measured using sensitive chemiluminescent multi-array technology. Results: HT patients were predominantly female (77.0%) with a median age of 56 years. Compared to controls, HT patients had higher median thyroid stimulating hormone (TSH) levels (2.215 vs. 1.705 μIU/mL, p = 0.025). Circulating autoantibodies were more prevalent in the HT group, with higher rates of APCA positivity (16.3% vs. 4.1%, p = 0.008) and atypical ANCA positivity (27.3% vs. 10.2%, p = 0.003). This suggests an increased risk for autoimmune gastritis and systemic inflammation. Additionally, HT patients with positive atypical ANCA showed elevated inflammatory cytokines, particularly interleukin-1 alpha (IL-1α), in female patients (p = 0.035). Conclusions: HT is significantly associated with a higher prevalence of circulating autoantibodies, such as APCA and atypical ANCA, which may indicate a heightened risk for autoimmune gastritis and broader autoimmune involvement. Detecting these autoantibodies in HT patients could serve as markers for more severe autoimmune dysfunction. These findings emphasize the need for proactive screening, especially in older patients and those with elevated A-TPO levels. Further research is essential to better understand the clinical implications and develop targeted management strategies for these patients.

Background: Thrombospondin-1 (TSP1) is a multimeric glycoprotein that is increasingly recognized as a mediator of metabolic, thrombotic, and inflammatory processes. Although TSP1 expression has been associated with adipose tissue dysfunction and insulin resistance, the precise relationship with obesity severity remains unclear. Endothelin-1 (ET1), another important regulator of vascular homeostasis, may also contribute to obesity-related cardiometabolic risk, with evidence suggesting sex-specific differences, including delayed onset in women. The study aimed to investigate circulating TSP1 and ET1 levels in a cohort of nondiabetic obese female adults, evaluate their associations with metabolic and inflammatory parameters, and determine whether these markers differ according to obesity severity and related disease risk. Methods: Fifty-five nondiabetic women with obesity and no history of cardiovascular events were enrolled at the Endocrinology Unit (“R. Dulbecco” Univ. Hospital, Catanzaro, Italy). Anthropometric and clinical data, together with hematological and coagulation parameters and metabolic indices (HOMA-IR, HbA1c, and lipid profile), were evaluated. TSP1 and ET1 concentrations were measured using automated enzyme immunoassays (ELISAs). The participants were stratified by BMI (30–34.9 vs. ≥35 kg/m²) into low-risk and moderate/high-risk obesity based on the WHO classification, and correlations between biomarkers and metabolic/inflammatory parameters were evaluated. Results: The median BMI was 33.7 kg/m², with 52% of participants having moderate/high-risk obesity (WHO Class II/III). A significant proportion (69.8%) showed insulin resistance (HOMA-IR > 2.5). TSP1 was positively correlated with white blood cell count (WBC, r = 0.354, p < 0.01), platelet count (PLT, r = 0.411, p < 0.01), and glycated hemoglobin (r = 0.391, p < 0.01), suggesting an association with both inflammation and glycemic control. ET1 was positively correlated with liver enzymes and triglycerides but negatively correlated with PLT and D-dimer. Women with moderate/high-risk obesity had significantly higher HOMA-IR, D-dimer, and inflammatory markers, in addition to a lower TSP1-to-PLT ratio. Conclusions: In this pilot study, TSP1 and ET1 levels tended to decrease with increasing obesity severity in women but were associated with distinct metabolic and inflammatory profiles. The results support the potential role of TSP1 as a biomarker for obesity-related cardiometabolic risk and highlight the complex interplay between TSP1, ET1, and obesity progression. Further studies may clarify whether targeting TSP1 can ameliorate chronic inflammation and insulin resistance in obesity and the potential sex-specific influences on these mechanisms.

Type 1 diabetes (T1D) is an autoimmune disease characterized by β-cell destruction as a common trait, in which variability in age at onset, progression rate, and clinical presentation shape heterogeneous phenotypes. Disentangling this heterogeneity is pivotal for a better understanding of clinical risk, evolution and a precision medicine approach to the disease. In this context, circulating islet autoantibodies, including the last discovered Zinc Transporter 8 autoantibodies (ZnT8A), represent crucial tools. This narrative review provides an overview of the current knowledge on ZnT8A in autoimmune diabetes from its structural and pathogenetic basis to its clinical relevance and therapeutic perspectives. A literature search was conducted in PubMed, Scopus, Google Scholar, and ResearchGate up to March 2026, that included preclinical, pediatric, adult, and assay-comparison studies. While the identification of ZnT8-targeted antigenic determinants is still ongoing, we discuss the pathogenic role of a newly identified specific class of antibodies directed against extracellular ZnT8 epitopes (ZnT8ecA). According to this finding, ZnT8ecA could facilitate the identification of an early phase of islet injury process, holding promise to provide a framework for new therapeutic strategies based on masking or modulating surface-exposed ZnT8 epitopes and interfering with the early stages of the disease. Moving from the role of ZnT8A in various clinical settings, we also focus on recent advancements in detection technologies, whose implementation accounts for invaluable contributions to diagnosis, disease risk, and, contextually, to a better understanding of autoimmune diabetes. Finally, we provide future perspectives, in T1D and T1-related diseases, for the potential clinical application of ZnT8A in early diagnosis, risk stratification and profiling, as well as in the development of targeted therapies as part of precision medicine.

Background: Celiac disease (CD) is frequently associated with autoimmune disorders such as Hashimoto’s thyroiditis and type 1 diabetes. Endocrine-specific autoantibodies may emerge during the course of CD, but their true prevalence and clinical relevance in children remain unclear. This study evaluated endocrine autoantibodies and inflammatory profiles in pediatric CD to inform a more tailored diagnostic approach. Methods: In this retrospective cross-sectional study, 240 consecutive children referred to a tertiary center for suspected CD and/or autoimmune endocrine disorders were included. CD was diagnosed according to ESPGHAN criteria. Laboratory evaluation comprised blood counts, metabolic parameters, thyroid function tests, thyroid autoantibodies (anti-TPO, anti-Tg), and type 1 diabetes-related autoantibodies (GAD, IA-2, ZnT8). A subgroup of children with CD (n = 28) underwent exploratory multiplex cytokine analysis. Results: Children with CD were slightly older and more often female than controls. Platelet counts were modestly lower in CD, while other hematologic parameters were similar. Thyroid autoimmunity prevalence did not differ significantly (anti-TPO: 2.7% in CD vs. 5.4% in controls; p = 0.348), and antibody titers and TSH levels were comparable. Anti-TPO positivity was associated with older age (p = 0.038), independent of CD status. Islet autoantibodies were similarly distributed between groups. Cytokine levels were not associated with tTG-IgA status; however, girls with CD showed higher IL-2, IL-4, and IL-10 levels than boys (all p < 0.05), with a trend toward higher IL-1α. Conclusions: In this pediatric cohort enriched for immune and endocrine concerns, CD was not linked to increased thyroid or pancreatic autoimmunity. Distinct sex-related differences in inflammatory profiles were observed, suggesting distinct immune patterns in girls with CD. These findings support a clinically driven rather than routine approach to endocrine autoantibody screening and warrant further studies on cytokine-based immune stratification.