Search Results (407)

Background: Traumatic head injury (THI) includes a diverse range of hemorrhagic brain lesions (HBL), which are distinct phenotypes with characteristic pathophysiological mechanisms. Computed tomography (CT) is the cornerstone of the initial assessment and diagnosis; however, its sensitivity is limited, especially in mild head injury. Blood-derived biomarkers, including Neuron-Specific Enolase (NSE) and S-100B, have been extensively studied; however, their efficacy in distinguishing HBL subtypes remains unclear. We evaluated whether circulating serum levels of S-100B and NSE can discriminate between distinct intracranial HBLs and extracranial hemorrhagic lesions (ECH). Methods: This is an interim analysis of a prospective, randomized, double-blind clinical trial including 434 adult patients with blunt THI. HBL phenotypes identified by CT scan included subarachnoid hemorrhage (SAH), subdural hematoma (SDH), epidural hematoma (EDH), and brain contusion (BC). Unique lesions were considered while overlapping lesions were excluded. Subgaleal hematoma (SGH) was included as an example of ECH. Serum S-100B was assessed within 6 h post-injury, while serum NSE was evaluated at admission, 24 h, and 48 h thereafter. Serum NSE and inflammatory cytokines were quantified in duplicates using a Human Magnetic Luminex 5-plex assay, while serum S-100B concentrations were measured separately. Serum epinephrine concentrations were quantified using an ELISA. Biomarker profiles were analyzed based on lesion phenotype, lesion multiplicity, injury pattern, and clinical outcomes, including hospital length of stay (HLOS) and the Glasgow Outcome Scale—Extended (GOSE). Results: Admission median S-100B levels were higher in patients with SAH (495 pg/mL) and lower in those with SGH (191 pg/mL); however, they did not show statistically significant difference among HBL phenotypes. They were significantly higher in patients with polytrauma TBI (420 pg/mL) compared to isolated TBI (258 pg/mL). Baseline and 48 h NSE concentrations were significantly higher in SDH (25,089 and 28,438 pg/mL) than in other THI lesions (p = 0.04). There were no statistically significant changes in NSE values over time across all THI lesions except for SDH in which they raised more after 48 h (p = 0.02). They had a significant drop in polytrauma over the time (p = 0.001). Compared to intracranial lesions, S-100 B levels were significantly lower in SGH and in skull fractures without intracranial hematomas. Both S-100B and NSE levels were elevated in individuals with unfavorable GOSE scores. Conclusions: In this secondary exploratory analysis, elevated serum NSE and S-100B levels discriminate between extra- and intracranial lesions and appear to represent distinct but complementary aspects of THI, indicating neuronal damage and its temporal evolution, and predicting clinical and functional outcomes. The present findings reflect association and not causation. Future studies incorporating larger or multicenter cohorts, volumetric imaging, and long-term outcomes are required to validate and refine biomarker-guided algorithms for personalized THI care. Full article

Introduction: Stereotactic radiotherapy (SRT) is increasingly used in oligometastatic non-small-cell lung cancer (NSCLC) and is known to elicit systemic immune effects, although the underlying mechanisms remain not fully understood. Methods: In this prospective pilot study, we evaluated plasma cytokine variations in 19 patients with oligometastatic or oligoprogressive NSCLC undergoing SRT. Peripheral blood samples were collected before treatment (T0) and one month after SRT (T1) and the concentrations of nine cytokines (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A and TNF-α) were quantified using a multiplex Luminex assay. Non-parametric tests and Cox regression models were used to investigate associations between cytokine levels, clinical variables, systemic treatments, and survival outcomes. SRT induced significant post-treatment increases in IFN-γ, IL-2, and IL-6, consistent with systemic pro-inflammatory activation and T-cell stimulation. Cytokine dynamics were influenced by patient- and tumor-related factors: female sex was associated with higher IL-2 and TNF-α levels; oncogene-addicted tumors showed lower IL-6 levels; and oligoprogressive disease exhibited attenuated cytokine variations compared with metachronous oligometastatic disease. Tyrosine kinase inhibitors were associated with globally reduced cytokine levels and blunted IL-1/IL-2 changes, whereas patients receiving immune checkpoint inhibitors displayed higher IL-2 and IL-6 concentrations and greater post-SRT increases in IFN-γ. Oncogene-addicted status and IL-12 variation emerged as independent predictors of overall survival and a composite model integrating these variables significantly stratified prognosis. Conclusions: These findings suggest that SRT triggers measurable systemic immune activation in oligometastatic NSCLC, which is further shaped by tumor biology, disease burden, and concomitant systemic therapies. Although limited by the small sample size, this study supports the feasibility and potential utility of cytokine profiling to refine patient selection and guide biomarker-driven combinations of SRT with targeted and immune-based treatments, warranting validation in larger prospective cohorts. Full article

The long asymptomatic period of clear cell renal cell carcinoma, which leads to delayed diagnosis and poorer prognosis, poses a global challenge. Chemokines play a pivotal role in immune regulation and tumor progression, making them promising biomarker candidates. This study aimed to evaluate the usefulness of the C-C motif chemokine ligand 3 (CCL3) and C-C motif chemokine ligand 7 (CCL7) by assessing their serum concentrations in 40 patients with stage G1 + G2 and stage G3 + G4 renal cancer, as well as in 58 healthy volunteers. Chemokine concentrations were measured using a multiplex Luminex assay and analyzed statistically, including receiver operating characteristic (ROC) analysis. Serum CCL3 concentrations were significantly elevated in ccRCC patients compared to controls and increased with tumor grade, with the highest levels observed in patients with advanced disease (G3+G4). In contrast, serum CCL7 levels were significantly lower in ccRCC patients than in healthy individuals, with no significant differences between tumor grade subgroups. ROC analysis revealed comparable diagnostic performance of CCL3 and CCL7, with CCL3 showing a slightly higher area under the curve. CCL3 showed high sensitivity, whereas CCL7 exhibited higher specificity than sensitivity, and a relatively high positive predictive value, consistent with its inverse regulation in ccRCC. These findings suggest that serum CCL3 and CCL7 are oppositely regulated in ccRCC and may serve as complementary non-invasive biomarkers for renal cancer detection. Full article

Background: Obesity is a recognized risk factor for developing breast cancer (BC), but factors involved remain unclear. We investigated if breast adipose tissue from healthy women, BRCA1/2 mutation carriers and BC patients, can stimulate BC cell line migration and activation. Methods: adipose tissue conditioned medium (ATCM), was prepared from breast adipose tissue from healthy subjects (naïve; group 1 (n = 20)), BRCA1/2 mutation carriers (group 2 (n = 22)) and BC patients (group 3 (n = 38)). ATCM effect on migration of BC cell lines MCF-7, SK-BR-3 and MDA-MB-231 was measured with xCELLigence (ACEA Biosciences, San Diego, CA, USA) cell migration assay. Activation of migration was determined by measuring filopodia activation. Migration and filopodia activation were related to body mass index (BMI) and BC subtypes. Luminex multiplex assay was performed to examine the secretory profile of adipose tissue. Results: ATCM from group 1 induced migration and filopodia activation in MCF-7 and MDA-MB-231, but not in SK-BR-3. ATCM from group 2 induced filopodia activation but no migration. ATCM from group 3 induced less migration in MCF-7 than ATCM from group 1. Higher BMI was associated with increased ATCM-induced activation in MCF-7 (group 1) and MDA-MB-231 (group 2). ATCM from group 1 and 2 showed a metabolic secretory profile, whereas group 3 showed higher pro-angiogenic and inflammatory cytokines. Conclusions: This study shows that breast adipose tissue from healthy women, BRCA1/2 mutation carriers and BC patients, can stimulate BC cell line migration and activation. This effect is related to BC subtype and BMI. These data improve insight in adipose tissue as factor in BC development. Full article

Background/Objectives: Neurotrophins are a family of structurally related growth factors known to play an important role in the physiology and pathophysiology of the central nervous system. In ischemic stroke, lower blood concentrations of brain-derived neurotrophic factor (BDNF) have been linked to worse outcomes. However, data regarding blood levels of other neurotrophins remain limited. Methods: Plasma levels of BDNF, NGF, NT-3 and NT-4 of 93 patients with ischemic stroke were measured using Luminex immunoassay at two time points: within 24 h from onset and on the seventh day. Clinical data regarding co-existing risk factors, National Institutes of Health Stroke Scale (NIHSS) score and mortality were collected and analyzed in relation to analytes. Results: BDNF levels at both time points were lower in patients with severe stroke and correlated negatively with NIHSS scores. No such associations were observed for NGF and NT-3. Patients who died had lower baseline BDNF, NT-4 and higher NT-3. Conclusions: A lower BDNF level, but no other neurotrophins, is associated with worse outcomes in ischemic stroke patients. NT-3 and NT-4 levels change in response to ischemic stroke. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by fluctuating disease activity and multi-organ involvement. The identification of reliable biomarkers that accurately reflect disease activity remains a significant clinical challenge, particularly in predicting disease flares. Chemokines are key mediators of immune cell recruitment and inflammation, making them promising candidates for disease activity monitoring. Therefore, we evaluated serum concentrations of CCL2, CCL4, CCL5, CXCL8, and CXCL10 and examined their associations with disease activity and clinical manifestations in patients with SLE. Patients and Methods: A total of 52 patients with SLE were enrolled in the study, of whom 15 (28.8%) had active disease (SLE Disease Activity Index [SLEDAI] ≥ 5) and 37 (71.2%) were in remission (SLEDAI < 5). An additional group of 12 age- and sex-matched healthy individuals without a family history of autoimmune diseases served as controls. All SLE patients fulfilled the 2019 EULAR/ACR classification criteria. Serum levels of the selected chemokines were measured in all participants using the Luminex Human Premixed Multi-Analyte Discovery Assay. Results: Serum concentrations of CCL2 and CCL4 did not differ between SLE patients and healthy controls, nor between active and inactive disease subgroups (p > 0.05, for all). In contrast, CCL5 levels were 34.30% higher in patients with SLE compared with controls (p = 0.013), with the strongest increase observed in the inactive disease subgroup as compared to controls (by 40.29%, p = 0.021). CXCL8 levels were markedly elevated in patients with active SLE relative to those in remission (by 123.30%, p = 0.011) and to healthy individuals (by 183.96%, p = 0.049). CXCL10 levels were higher in both active and inactive SLE groups compared with controls (increase of 180.80%, p < 0.001 and increase of 100.80%, p = 0.018, respectively). No differences in chemokine levels were detected between patients with renal flares and those with non-renal flares, nor among patients in remission with and without a history of lupus nephritis (p > 0.05, for all). CXCL8 and CXCL10 correlated positively with disease activity scores, inflammatory markers, and several immune parameters, indicating their relevance to ongoing inflammatory processes (p < 0.05, for all). CCL5 was associated with complement components C3 (r_S = 0.36, p = 0.008) and C4 (r_S = 0.38, p = 0.006), while CXCL10 showed negative correlations with white blood cell (r_S = −0.34, p = 0.013), lymphocyte counts (r_S = −0.36, p = 0.008) and neutrophils (r_S = −0.32, p = 0.019). In the longitudinal follow-up of patients in remission (median follow-up time of 5.5 years), baseline chemokine levels did not predict subsequent disease flares among SLE patients who were inactive as the study baseline (p > 0.05, for all). Conclusions: In our study, serum levels of CXCL8 and CXCL10 reflect disease activity and systemic inflammation in SLE, supporting their potential value as biomarkers for monitoring ongoing immune activation. Baseline concentrations of the examined chemokines did not predict future disease flares, indicating their limited utility in this context. Full article

The aim of this study was to compare the responses of normal human gingival epithelial cells (HGEpiC) and oral squamous cell carcinoma cells (OECM-1) to apigenin, a natural flavonoid, focusing on redox balance, autophagy, and apoptosis. This study is among the first to directly compare apigenin-induced responses in normal and cancerous oral epithelial cells. Cells were exposed to apigenin for 24 or 48 h, with untreated cells as controls. Mitochondrial activity, ATP, ROS (H₂O₂), and GSH were measured. Proliferation and morphology were monitored using HoloMonitor^® M4. Autophagy was assessed by fluorescent vacuole labeling, and apoptosis-related proteins (p-AKT, p-BCL-2, p-p53, p-JNK, caspase-8/9) by Luminex assay. Late apoptosis was evaluated by caspase-3/7 activity. Apigenin elicited a differential response: in HGEpiC cells, it was non-cytotoxic and increased metabolic activity, induced a moderate ROS increase, and activated autophagy as a pro-survival mechanism; in contrast, OECM-1 cells exhibited a significant reduction in metabolic activity, a marked ATP decrease at 24 h, and a pronounced ROS increase. These alterations were associated with reduced autophagy and decreased p-JNK signaling. These findings indicate that apigenin exerted no harmful effects on HGEpiC cells, while inducing redox imbalance in OECM-1 cells, highlighting a context-dependent cellular response. Full article

Background/Objectives: Chronic lung allograft dysfunction (CLAD) remains the leading cause of late graft failure after lung transplantation (LuTX). De novo donor-specific anti-HLA antibodies (dnDSA), especially HLA-DQ, have been implicated; we assessed associations between dnDSA (class and specificity) and CLAD after LuTX. Methods: We retrospectively analyzed all LuTX recipients transplanted from 2005–2018 at a single center (n = 585). dnDSA were measured by Luminex single-antigen bead assays (MFI > 1000) at 1, 3, 6, and 12 months and at least annually thereafter. CLAD was defined by ISHLT criteria; time-to-event comparisons used log-rank testing. Results: dnDSA developed in 151/585 recipients (25.8%), predominantly class II (129/585; 22.1%); class I dnDSA occurred in 52/585 (8.9%). CLAD occurred more frequently in dnDSA-positive than dnDSA-negative recipients (64/151; 42.4% vs. 109/434; 25.1%; p < 0.0001). Rejection-attributed death was higher in dnDSA-positive recipients (19/151; 11.3% vs. 25/434; 5.3%; p = 0.01). Both class I and class II dnDSA were associated with higher CLAD rates (log-rank p < 0.001 each). Locus-specific analyses identified HLA-DQ dnDSA as strongly associated with CLAD (p < 0.0001); DQ7 was the most frequent specificity (n = 44) and showed the strongest association (p < 0.0001). Conclusions: dnDSA after LuTX were associated with increased CLAD incidence and rejection-attributed mortality, with a prominent association for HLA-DQ—particularly DQ7. Full article

Background: Pulmonary inflammation is a widely recognized characteristic of active tuberculosis (TB). Although standard TB treatment is effective, a substantial proportion of mycobacteriologically cured TB patients experience persistent pulmonary inflammation, which can lead to long-term lung impairment, post-tuberculosis lung disease (PTLD) and potentially TB recurrence. Methods: We conducted a case–control study to compare host serum biomarker profiles in individuals with minimal (TLG < 50 SUVbw*mL, n = 37) versus extensive (TLG ≥ 50 SUVbw*mL, n = 34) persistent lung inflammation following completion of standard drug-sensitive TB treatment. Lung inflammation was measured by 18F-FDG PET/CT scan using total lung glycolysis (TLG) as a surrogate marker. All participants had negative sputum cultures at four months of TB treatment, and blood samples were collected at treatment completion (month six). A Luminex^® multiplex assay performed on the Bio-Plex^® 200 platform was used to analyze 48 host serum biomarkers involved in cytokine/chemokine signaling. Results: Following multiple t-test analysis, fifteen biomarkers were significantly elevated (p < 0.05) in participants with extensive persistent lung inflammation compared to those with minimal inflammation. Among these, 14 demonstrated potential as discriminatory markers, with area under the curve (AUC) values ranging from 0.707 to 0.806, sensitivities ranging from 47.06% to 73.53%, and specificities ranging from 70.27% to 83.78%. Notably, 13 of these 16 candidate biomarkers significantly correlated with TLG values, further supporting their potential clinical utility. Conclusion: We report associations between serum inflammatory mediators and persistent pulmonary inflammation following mycobacterial clearance in TB patients, highlighting their potential as diagnostic biomarkers that could potentially meet the target product profile (TPP) criteria. Full article

Circulant follicular helper T cells (cTfh) are a specialized subset of CD4⁺ T cells that induce immunoglobulin class switching and antibody secretion in plasma cells through the production of IL-21. To investigate the role of cTfh-like cells in the development of Sjögren’s disease (SjD), we analyzed the circulating Tfh-like cells, their production of IL-21 and IL-4, and the co-expression of ICOS, CXCR5, and CCR9 by flow cytometry, and evaluated their association with clinical characteristics of the disease. Percentages of CD4⁺ IL-21⁺ CXCR5⁺ ICOS⁺ CCR9⁺ IL-4⁺ T cells were analyzed in peripheral blood samples from 20 healthy controls (HCs) and 19 patients with SjD. Serum levels of IL-1β, IL-4, IL-6, IL-21, and sCD40L were assessed using a Luminex assay. Laboratory data included anti-Ro/La antibodies, immunoglobulin levels (IgA and IgG), focus score, disease duration, and ESDDAI/SSDDI scores. Decreased frequencies of CXCR5⁺ IL-21⁺ T cells and CCR9⁺ IL-4⁺ T cells were observed in the peripheral blood of patients with SjD. Heatmap analysis was used to identify correlations between cTfh-like cells and clinical parameters. Elevated proportions of cTfh-like cells were positively correlated with disease severity, inflammatory markers, and autoantibody production. High-dimensional analysis identified distinct subpopulations with differential expression of ICOS, CXCR5, CCR9 and IL-21, suggesting heterogeneity of these cells in SjD and their involvement in disease pathogenesis. Full article

Background: Pancreatic Ductal Adenocarcinoma (PDAC) has a dismal five-year survival rate of 13% and is closely associated with cachexia. Cancer cachexia is a multifactorial syndrome characterized by irreversible wasting of skeletal muscles, fat loss and systemic inflammation. While cachexia is known to confer resistance to immune checkpoint inhibition in several cancers, the bidirectional relationship between cachexia and the immune system in PDAC remains unclear, necessitating the development of novel preclinical models. Our laboratory has characterized a novel pancreatic cancer cachexia model in C57BL/6J mice by utilizing the pancreatic cancer cell line called KPCL-4 derived from KPC-LSIY mice (Kras^LSL-G12D/+Tp53^LSL-R172H/+Pdx1-Cre/R26^LSL-LSIY). Methods: KPCL-4 cells were orthotopically injected into the pancreas of male and female C57BL/6J mice and hallmarks of cachexia were assessed at endpoint by measurement of tumor weight, terminal tumor-adjusted body weight, skeletal muscle, adipose tissue, liver and spleen masses, proteolytic markers and grip strength. Plasma cytokine and chemokine concentrations were quantified by Luminex assay and high-dimensional flow cytometry was used to investigate changes in tumor-infiltrating immune populations. Results: We observed a sex bias in cachexia presentation despite similar tumor weights in male and female mice, whereby males exhibited a >5% decrease in terminal tumor-adjusted body weight (p < 0.001), >50% fat loss (p < 0.001), upregulation of proteolytic markers in skeletal muscles (p < 0.01) and reduction in skeletal muscle mass (p < 0.05), function (p < 0.01) and cross-sectional area (p < 0.0001) whereas females demonstrated conserved skeletal muscle mass with 33% fat loss (p < 0.05), reduction in muscle cross-sectional area (p < 0.0001) and splenomegaly (p < 0.01). While intra-tumoral immune populations did not exhibit sex-specific differences, plasma cytokine concentrations were differentially upregulated in males and females, suggesting functional differences in immune cells as potent drivers of sex bias in KPCL-4-driven cachexia. Conclusions: The KPCL-4 orthotopic PDAC model exhibits prominent hallmarks of cachexia and serves as a novel platform for investigating the complex interplay between cancer cachexia and immunomodulation. Full article

Postprandial inflammation, characterized by elevated cytokines, is linked to metabolic diseases. Polyphenol-rich fruits like strawberries possess anti-inflammatory properties that may help reduce this response. Because clinical studies are often costly and time-consuming, this study aimed to develop an in vitro model using whole blood to examine the effect of bioactive components such as polyphenols on postprandial inflammation. Whole blood from healthy adults was exposed to lipopolysaccharides (LPS) and high glucose concentrations (250/500 mg/dL), as well as strawberry extract (100 ng/mL). Cytokines (interleukin-6 and -1 beta; IL-6, IL-1β, and Tumor Necrosis Factor-alpha; TNF-α) were quantified using the Luminex multiplex assay. High glucose levels caused non-significant increases in IL-6 (p > 0.05), while strawberry extracts significantly reduced LPS-induced cytokines (p < 0.05). These findings demonstrate the potential of using whole blood in vitro systems to model inflammation and to explore the anti-inflammatory effects of fruit components such as polyphenols from strawberries. Full article

Pancreatic cancer remains one of the most aggressive digestive neoplasms, especially due to late diagnosis. The aim of our study was to investigate cytokeratin-19 fragments (CYFRA 21-1), osteopontin (OPN), and human epididymis protein 4 (HE4) clinical significance in pancreatic adenocarcinoma. Our research is a single-center cross-sectional prospective study that included sixty hospitalized patients diagnosed with pancreatic adenocarcinoma and fourteen controls. CYFRA 21-1, OPN, and HE4 were tested in all participants using Luminex x MAP technology. Serum CYFRA 21-1 levels were weakly correlated with those of OPN (r = 0.302; p = 0.009), HE4 (r = 0.485; p < 0.001), and carbohydrate antigen (CA) 125 (r = 0.376; p = 0.037). Similarly to CA 19-9 and CA 125, the serum OPN levels were higher in patients with pancreatic cancer when compared to controls, 3.37 (1.84; 9.12) ng/mL versus 1.59 (1.09; 2.51) ng/mL; p = 0.003. However, in multivariate analysis, the OPN was not an independent predictor for pancreatic cancer. Further, the receiver operating characteristic (ROC) curve analysis identified CA 19-9 as the biomarker with the highest diagnostic accuracy, while CYFRA 21-1, OPN, and HE4 did not reach clinically meaningful results. Further, the CYFRA 21-1 levels were significantly higher in cases subjected to significant weight loss before admission. Full article

COVID-19 and influenza A (FluA) cause severe respiratory infections in elderly patients, with cytokine dysregulation playing a central role. Direct comparative data in older adults remains limited. We aimed to characterize cytokine dynamics and their prognostic value in hospitalized elderly patients with COVID-19 vs. FluA. We performed a prospective cohort study including adults ≥ 60 years hospitalized with respiratory failure due to COVID-19 or FluA between March 2023 and March 2024. Serum IL-1β, IL-6, IL-10, IL-17A, IL-34, MCP-1, and CXCL10 were measured on Day 1 and Day 5 of hospitalization using Luminex^®. Cytokines and associations with non-invasive ventilation (NIV) were assessed by ROC analysis and multivariate logistic regression. 83 patients were included (39 COVID-19, median age 79 years; 44 FluA, median 77 years). At Day 1, COVID-19 exhibited significantly higher IL-6, IL-10, and CXCL10; FluA showed an attenuated cytokine response. At Day 5, cytokines declined in both groups. Baseline IL-6 independently predicted NIV (adjusted OR 3.02), whereas higher MCP-1 was associated with reduced NIV requirement. Early cytokine differences between COVID-19 and FluA are evident in elderly patients, but values converged by Day 5. IL-6 remains an informative early predictor of respiratory deterioration; MCP-1 may reflect a regulated innate response. Full article

Background: Experimental autoimmune thyroiditis is an important animal model for studying Hashimoto’s thyroiditis. Our aim was to develop the model using CBA/J-DR3 mice expressing human HLA-DR3, which is associated with autoimmune thyroiditis in humans, to better simulate human autoimmune thyroiditis. Such a humanized model can be used to test specific antigen therapies for autoimmune thyroiditis. Methods: CBA/J-DR3 mice were produced by back-crossing B6-DR3 mice to the CBA/J background. Female CBA/J-DR3 mice were immunized with human thyroglobulin (Tg) in complete Freund’s adjuvant on days 0 and 7. On day 21, mice were sacrificed, blood collected, spleen and thyroid harvested for analysis. Splenocytes were analyzed for T cell responses to Tg and its major T-cell epitope in human autoimmune thyroiditis, Tg.2098. Serum anti-thyroglobulin antibodies were measured by ELISA, and thyroid-stimulating hormone was measured using the Luminex assay. Thyroid histology and immunohistochemistry were examined. Results: Immunized CBA/J-DR3 mice showed significant T cell proliferation in response to Tg (stimulation index 3.4 ± 4.5) and Tg.2098 (1.5 ± 0.7). Anti-thyroglobulin antibody levels were elevated in immunized mice when compared to control mice (2.05 ± 0.75 vs. 0.15 ± 0.06, p < 0.0001). T cells demonstrated higher reactivity to thyroid antigens by enhanced production of pro-inflammatory cytokines. Thyroid immunohistochemistry revealed mild CD3-positive T-cell infiltration. Conclusions: This novel humanized CBA/J-DR3 mouse model of Hashimoto’s thyroiditis demonstrates key features of human autoimmune thyroiditis. The HLA-DR3 background and the immune response to Tg and Tg.2098 enhance translational relevance, making this a valuable model for studying thyroid disease pathogenesis and testing targeted immune-modifying therapies. Full article