Search Results (188)

Autoimmune diseases arise from a breakdown of immune tolerance and complex interplay of genetic susceptibility, environmental triggers, tissue-specific immune responses, microbiota, and regulatory pathways. Mouse models remain essential for dissecting these mechanisms, but no single model fully reproduces the heterogeneity, chronicity, and immune complexity of autoimmune disease in humans. This review summarizes classical murine and humanized mouse models used to study inflammatory bowel disease (IBD), multiple sclerosis (MS), type-1 diabetes (T1D), and rheumatoid arthritis (RA). We also highlight disease-specific scoring systems, including clinical indices, histopathology, imaging, cytokine profiling, autoantibody assessment, and human immune-cell readouts, as essential tools for standardized interpretation. Conventional murine models provide experimental control and mechanistic clarity, whereas humanized models improve assessment of human immune responses, patient-specific biology, and therapeutic translation. However, humanized systems remain limited by incomplete immune reconstitution, graft-versus-host disease, donor variability, cost, and incomplete tissue architecture. By providing a comparative framework spanning both conventional and humanized models, this review aims to guide informed model selection tailored to specific research questions in autoimmune disease biology and translational therapeutic development. Full article

Background: Antinuclear antibodies (ANA) can be detected in patients with rheumatoid arthritis (RA) and pose many diagnostic challenges, especially when RA presents an atypical course and requires differentiation from other systemic connective tissue diseases (sCTDs). This study assessed ANA fluorescence patterns and immunoblot profiles, as well as the relationships between ANA titers, antibody expression intensity, and markers of disease activity in patients with RA. Methods: This single-center, cross-sectional, observational study included 81 RA patients (53 ANA-positive) meeting the 2010 ACR/EULAR classification criteria. ANA titers and fluorescence patterns were assessed using indirect immunofluorescence. Anti-extractable nuclear antigen (ENA) autoantibody profiles and expression intensity were assessed using immunoblot analysis. Demographic, clinical, and laboratory data were obtained. Spearman’s rank correlation coefficient was used to analyze the relationship between ANA titers and selected variables. Univariate and multivariate logistic regression analyses were performed to identify factors associated with ANA positivity. Results: The cohort consisted primarily of women (86.4%) with moderate disease activity. ANA fluorescence patterns were heterogeneous, with nucleolar and homogeneous patterns most frequently observed. Immunoblot analysis also revealed diverse autoantibody profiles without a clearly dominant specificity. Ro-52, SS-A, and Sm antibodies were detected more frequently, although their prevalence remained relatively low. No statistically significant correlations were found between ANA titers and inflammatory markers, serological parameters, or disease activity indices. Conclusions: RA patients with positive ANA demonstrated marked immunological heterogeneity, without concomitant symptoms of sCTD. A positive result in RA may reflect generalized immune dysregulation rather than a distinct clinical subtype. Further studies with larger cohorts are needed to clarify the clinical significance of ANAs in rheumatoid arthritis. Full article

Autoimmune hepatitis (AIH) lacks a disease-specific diagnostic biomarker, particularly for patients who present with acute onset, normal IgG levels, or seronegative profiles. Recent advances in high-throughput autoantibody profiling technologies have enabled the systematic discovery of novel AIH-associated autoantigens. This review summarizes emerging autoantibodies that have been identified through proteome-wide screening approaches, including human protein microarrays and phage immunoprecipitation sequencing. Particular attention is given to anti-docking protein 2 (DOK2) and anti-mitochondrial ribosomal protein S27 (MRPS27) antibodies, which have shown promising diagnostic performance. Importantly, the combined assessment of these autoantibodies markedly improves the diagnostic sensitivity for AIH and may be useful for screening or clinical triage, although its reduced specificity limits its use as a stand-alone confirmatory test. We also discuss how the integration of serological biomarkers with molecular pathology and spatial immune analysis may advance the understanding of AIH pathogenesis. These developments highlight the potential of proteome-wide autoantibody discovery to refine diagnostic strategies for AIH and provide new insights into disease mechanisms. Full article

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. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is characterized by diverse clinical presentations and complex immunological mechanisms. This study aimed to characterize patient serology associated with disease activity scored using the systemic lupus erythematosus disease activity index (SLEDAI) and investigate the molecular signature of complement activation (measured through C3dg, a complement breakdown product) in SLE patients utilizing high-throughput mass spectrometry and autoantibody profiling. Methods: Plasma samples from 39 SLE patients in four mutually exclusive groups based on either disease activity scores (high/low SLEDAI) or complement activation levels (high/low C3dg) were analyzed using rapid LC-MS/MS, followed by unsupervised and supervised protein expression analysis. Complement activation was evaluated by measuring C3dg levels, and disease activity was scored using SLEDAI. Autoantibody reactivities were profiled using global autoantibody protein microarrays. Data are available via ProteomeXchange with identifier PXD066214. Results: Differential proteomic analyses revealed 25 proteins associated with SLE disease activity (high vs. low SLEDAI scores) and 25 proteins linked to complement activation levels (high vs. low C3dg). Enriched pathways indicated that adaptive immune response, classical complement activation, and immunoglobulin production correlated with disease activity, while complement activation and coagulation cascades were primarily associated with complement activation levels. Autoantibody profiling highlighted distinct reactivity patterns between subgroups, suggesting varying degrees of immune-mediated tissue damage. Conclusions: In this study, disease activity and complement activation markers were associated with overlapping yet non-identical plasma proteomic patterns in SLE. These findings support the feasibility of rapid mass spectrometry-based proteomics and autoantibody profiling for generating candidate molecular signatures in SLE. These findings serve as exploratory signatures that require validation in larger independent cohorts before they can be considered for clinical stratification and decision-making. Full article

Background: Systemic sclerosis (SSc) is an autoimmune disease with interstitial lung disease (ILD) representing the leading cause of mortality. Diaphragmatic muscle impairment, which may contribute to respiratory dysfunction, is underexplored in SSc. Objective: This study aimed to assess diaphragmatic thickness using HRCT in patients with SSc-ILD and to investigate whether this parameter correlates with disease severity and clinical outcomes. Methods: We conducted a multicentric retrospective observational study that included 161 participants: 69 with SSc-ILD and 92 matched controls without pulmonary disease. Preliminary findings from this cohort were previously communicated as a conference abstract at EULAR 2024. Diaphragmatic thickness was measured on axial and coronal CT images at the celiac axis level by two independent radiologists. Clinical and functional parameters were collected, including forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO), echocardiographic findings, and 6 min walking test performance. Results: The left hemidiaphragm was significantly thinner in patients with SSc-ILD compared with controls (2.98 ± 1.04 mm vs. 3.44 ± 0.97 mm; p = 0.004), while the right hemidiaphragm showed a non-significant trend toward reduction (3.21 ± 1.09 mm vs. 3.52 ± 1.05 mm; p = 0.072). Thinning of the right hemidiaphragm correlated significantly with lower FVC (p < 0.05). ROC analysis identified an optimal left diaphragm cut-off of ≤3.115 mm (AUC = 0.635, 95% CI: 0.556–0.709, sensitivity = 66.7%, specificity = 60.9%). No associations were found with the autoantibody profile, disease duration, or treatment. Interobserver reliability was excellent (Bland–Altman mean difference −0.002 mm, p = 0.95). Conclusions: HRCT-measured left hemidiaphragm thickness is significantly reduced in patients with SSc-ILD compared with controls, and right hemidiaphragm thickness correlates with impaired lung function. Although its discriminative performance is modest (AUC 0.635), this parameter may serve as a supplementary zero-burden addition to routine HRCT evaluation alongside pulmonary function tests. The retrospective cross-sectional design precludes conclusions about causality or prognosis; prospective studies incorporating concurrent functional diaphragm assessment are warranted. Full article

Glaucoma is a chronic progressive optic neuropathy and one of the leading causes of irreversible blindness worldwide. Although elevated intraocular pressure remains the most important modifiable risk factor, increasing evidence suggests that immune dysregulation and autoimmune responses also contribute substantially to disease onset and progression. Clinical studies across different glaucoma subtypes have identified subtype-dependent immune abnormalities, including altered serum autoantibody profiles, dysregulated cytokine and chemokine expression, and changes in peripheral immune cell subsets. Experimental and translational studies further indicate that multiple immunopathogenic mechanisms are involved in glaucomatous neurodegeneration, including glial cell-mediated immune responses, activation of pattern recognition receptor signalling pathways, adaptive immune responses, and complement cascade dysregulation. These processes may interact to sustain chronic neuroinflammation, promote retinal ganglion cell injury, and accelerate optic nerve degeneration. Importantly, a better understanding of immune involvement in glaucoma has generated growing interest in immunomodulatory therapy as a potential strategy beyond intraocular pressure lowering. Targeting microglial activation, inflammatory signalling pathways, adaptive immune imbalance, and complement-mediated injury has shown neuroprotective potential in animal or in vitro models, whereas clinical evidence in glaucoma patients remains limited. These findings may provide preliminary directions for future therapeutic development. In this review, we summarise the current clinical evidence linking glaucoma with autoimmunity, discuss the major immune mechanisms implicated in disease pathogenesis, and highlight recent advances in immunomodulatory therapeutic strategies. Elucidating the immune basis of glaucoma may help pave the way for more precise and effective treatments for this complex optic neuropathy. We believe that immune dysregulation in glaucoma functions as a context-dependent amplifier of retinal ganglion cell injury rather than a uniform primary driver, with innate (microglia/astrocytes), adaptive (T/B cells, HSP-specific immunity), and complement pathways interacting to sustain neuroinflammation and neurodegeneration. This integrated immune response contributes to subtype- and stage-specific vulnerability, and targeting these maladaptive immune mechanisms represents a promising, precision-guided strategy for neuroprotection beyond intraocular pressure lowering. Full article

The hypothesis that Group A beta-haemolytic Streptococcus (GAS) triggers an autoimmune cascade targeting basal ganglia dopaminergic circuits—producing obsessive–compulsive disorder (OCD), tic disorders, or chorea depending on the receptor subtype involved—is biologically compelling and supported by emerging molecular evidence. Yet PANDAS has remained a diagnostic conundrum since its original description in 1998, with ongoing uncertainty surrounding diagnostic criteria, the interpretation of streptococcal serology, and the distinction from primary neurodevelopmental disorders. This study aimed to review the diagnostic challenges of PANDAS, with focus on streptococcal serology interpretation, advances in dopamine receptor autoantibody biology, the genetic epidemiology of primary tic disorders, and the differential diagnosis of acute neuropsychiatric presentations in children. A structured narrative review was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Library for publications from 1998 to early 2025 addressing PANDAS, PANS, streptococcal antibodies, childhood movement disorders, autoimmune encephalitis, and the genetics of tic disorders. No currently available biomarker—including ASO, anti-DNase B, anti-basal-ganglia antibodies, or the Cunningham Panel—has demonstrated adequate individual-level diagnostic accuracy for PANDAS. Emerging molecular evidence identifies anti-D1R autoantibodies, acting via G protein-and beta-arrestin-mediated signalling, as candidate biomarkers for PANDAS/PANS neuropsychiatric phenotypes, and anti-D2R autoantibodies for Sydenham chorea movement phenotypes; independent replication in unselected populations is required. Primary tic disorders carry heritability estimates of 50–80% and first-degree familial risk ratios of approximately 18-fold in large population-based cohorts. Prospective blinded studies have not demonstrated a consistent population-level association between GAS infections and tic or OCD exacerbations: PANDAS and PANS remain diagnoses of exclusion. The high background prevalence of both GAS exposure and primary neurodevelopmental disorders in overlapping paediatric age ranges creates conditions for incidental temporal co-occurrence. In the absence of validated molecular biomarkers, diagnostic imprecision carries direct clinical consequences: children may be exposed to treatments with significant risk profiles—including IVIG, plasma exchange, and prolonged antibiotic prophylaxis—while evidence-based therapies are delayed. A stepwise diagnostic approach incorporating the full differential diagnosis is both an epistemological and a patient safety imperative. Full article

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disorder arising from the convergence of genetic susceptibility, epigenetic remodeling, environmental exposures, and dysregulated immune networks. Although traditionally characterized by autoantibody production and immune complex mediated tissue injury, advances in genomics, systems immunology, and multi-omics profiling have revealed that lupus represents a multilayered failure of immune homeostasis driven by interconnected molecular circuits. Genetic variants enriched in regulatory immune enhancers establish a permissive transcriptional landscape that sensitizes innate nucleic acid sensing pathways and interferon signaling. Epigenetic remodeling further amplifies inflammatory transcriptional programs, while environmental triggers such as ultraviolet radiation and viral infection initiate bursts of nucleic acid release and immune activation. Defective apoptotic cell clearance, mediated in part by scavenger receptor dysfunction and complement abnormalities, increases the availability of immunogenic nucleic acids that engage pattern recognition receptors and drive chronic type I interferon production. This interferon-dominated environment rewires immune cell metabolism, alters differentiation trajectories of T and B lymphocytes, and sustains autoreactive immune circuits. Emerging multi-omics studies reveal distinct molecular endotypes defined by interferon signatures, metabolic states, and immune cell composition, highlighting the heterogeneity of disease mechanisms across patients. In this review, we integrate genetic, epigenetic, metabolic, and immunological insights to propose a systems-level model of lupus pathogenesis in which defective debris clearance, nucleic acid sensing, interferon amplification, and metabolic reprograming form a self-reinforcing pathogenic network. Understanding this integrated molecular architecture provides a foundation for biomarker-guided therapeutic strategies and precision medicine approaches aimed at disrupting the key nodes that sustain chronic autoimmunity in SLE. Full article

The autoantibody reactome refers to the multidimensional repertoire of antibody reactivities against self-antigens across the human proteome or selected antigenic compartments. This offers a scalable systemic layer for precision immunology across spontaneous autoimmunity and treatment-induced immune toxicity. Autoimmune diseases and immune-related adverse events (irAEs) share major features of dysregulated immunity, yet clinically useful tools for risk stratification, early detection, endotyping, and treatment guidance remain limited and slow. A central challenge is that tissue pathology is highly informative but not uniformly accessible across diseases and organ systems, whereas routine serology captures only a narrow fraction of immune heterogeneity. In this perspective, I argue that a global autoantibody reactome can serve as a central unifying framework linking systemic immune history, tissue pathology, and clinical trajectories across autoimmune disorders and irAEs. Rheumatoid arthritis (RA) provides a strong prototype because its serological diversity, major role of post-translationally modified autoantigens, and marked synovial heterogeneity allow reactome features to be interpreted against tissue biology. Immune checkpoint inhibitor-associated inflammatory arthritis serves as an illustrative rheumatic irAE and a model of treatment-induced immune dysregulation with clear opportunities for longitudinal blood-based profiling. Spatial transcriptomics and proteomics are therefore positioned not as stand-alone solutions, but as mechanistic tools that can decode reactome-defined immune states within tissue microenvironments where tissue is accessible. Clinical translation will require integration of autoantibody reactomes with tissue, circulating proteomic, imaging, genetic, and clinical data through transparent multimodal models, as well as a shift from exploratory resources such as AAgAtlas toward analytically validated and clinically interpretable biomarker panels for risk prediction, endotyping, monitoring, and biomarker-guided intervention. This perspective outlines technical and strategic steps toward clinically actionable decision support, including risk stratification before ICI initiation and treatment guidance for patients who develop ICI-induced inflammatory arthritis, through integration of autoantibody reactome profiling, spatial omics and transparent multimodal AI. Full article

Radon-222, a naturally occurring radioactive gas, is the second leading cause of lung cancer globally, after tobacco use. When inhaled, its decay products, especially polonium-218 and polonium-214, emit high-energy alpha particles that induce dense DNA damage in the bronchial epithelium. Because ambient radon measurements often vary significantly over time and across locations, they provide limited insight into individual exposure levels. This suggests the urgent need for biological markers that can accurately indicate internal dose and early signs of lung cancer development. This review offers an extensive overview of biomarkers associated with radon exposure, from internal dosimetry to early biological responses. It covers internal dose markers (e.g., radon progeny in air and ²¹⁰Po/²¹⁰Pb in bones and teeth), molecular and cytogenetic indicators of effective dose (such as chromosomal aberrations, γ-H2AX foci, and DNA adducts), and early effect markers (including somatic mutations, epigenetic changes, miRNA profiles, and autoantibody signatures). The review highlights translocations detected via FISH, discussing those that are stable over time versus those that are transient. It also evaluates the reliability and practicality of these biomarkers in occupational and residential settings, noting how smoking complicates causal inference due to overlapping mutation pathways. Finally, it suggests that integrating multi-omics technologies could improve the precision of biomarker panels. Full article

Background/Objectives: Primary Sjögren’s disease is a systemic autoimmune disease characterized by chronic inflammation of exocrine glands and heterogeneous clinical manifestations. There remains a need for objective, non-invasive biomarkers that reflect local glandular involvement and disease-related immune activity. Methods: This observational cross-sectional case–control study included 34 patients fulfilling the 2016 ACR/EULAR classification criteria for primary Sjögren’s disease and 34 healthy controls between December 2024 and February 2025. Unstimulated whole-saliva samples were collected in the morning using the passive drool method, and salivary galectin-9 concentrations were measured via the enzyme-linked immunosorbent assay. Disease activity and symptom burden were assessed using validated indices, and receiver operating characteristic analysis was performed to evaluate discriminatory performance. Results: Salivary galectin-9 levels were significantly higher in patients with primary Sjögren’s disease compared with healthy controls. However, no significant associations were observed between salivary galectin-9 levels and disease activity scores after correction for multiple comparisons, nor with patient-reported symptoms, autoantibody profiles, Schirmer test results, or minor salivary gland biopsy findings. Salivary galectin-9 demonstrated limited discriminative ability between patients and controls. Conclusions: Salivary galectin-9 levels were elevated in primary Sjögren’s disease and may be associated with local glandular immune processes. Further prospective studies are needed to determine their clinical relevance. Full article

Arrhythmogenic cardiomyopathy (ACM) is a genetic myocardial disorder marked by progressive cardiomyocyte loss, fibro-fatty replacement, ventricular arrhythmias, and risk of sudden cardiac death. Traditionally considered a structural and electrical disease driven by desmosomal dysfunction, emerging evidence redefines ACM as an inflammatory cardiomyopathy in which immune activation plays a central role. This review integrates genetic, molecular, experimental, and clinical data to highlight inflammation as a unifying feature of ACM. Desmosomal gene variants impair cell adhesion and also activate cardiomyocyte-intrinsic inflammatory pathways, including nuclear factor of kappa B (NFκB) and glycogen synthase kinase 3β (GSK3β) signaling, promoting cytokine release, immune cell recruitment, and fibrotic remodeling. Preclinical studies suggest inflammation precedes structural changes, indicating it may be an initiating event rather than a secondary response. Clinical and pathological findings support this model, with inflammatory infiltrates, circulating cytokines, and autoantibodies observed across disease stages. These processes often present as episodic “hot phases” resembling myocarditis, thus complicating diagnosis. The inflammatory landscape involves both innate and adaptive immunity, along with stromal and neuronal remodeling, contributing to arrhythmogenesis through gap junction disruption, calcium-handling abnormalities, and fibrosis. Environmental factors such as exercise, stress, and metabolic disturbances further modulate inflammatory pathways and disease expression. Therapeutically, this evolving perspective supports immunomodulatory approaches, including inhibition of NFκB, GSK3β, and cytokine signaling. Early clinical data on immunosuppressive and cytokine-directed therapies are promising, especially during active inflammatory phases, while gene-based strategies specifically address the underlying genetic defects. In conclusion, ACM should be recognized as an inflammatory cardiomyopathy shaped by interactions between genetic susceptibility and immune dysregulation. Integrating genetic and immunologic profiling may improve diagnosis, risk stratification, and treatment, ultimately leading to refined personalized therapeutic strategies. Full article

Objective: Current knowledge surrounding the diagnosis and mechanisms that result in immune checkpoint inhibitor-associated diabetes (ICI-DM) remain to be fully defined. We present clinical vignettes of patients that have presented to our hospital to illustrate the heterogenous clinical profiles that patients with ICI-DM can experience. We also provide an update on ICI-DM, focusing on current and future perspectives and emerging therapies. Methods: We performed a retrospective review of the electronic records of five ICI-DM patients who presented to St. Vincent’s Hospital Melbourne between 2020 and 2024, with patients identified from the hospital endocrinology and oncology databases. We also performed a literature review via a PubMed search using the keywords “checkpoint inhibitors” and “diabetes” between the years 2015 and 2025 to allow us to collate a descriptive review on ICI-DM. Results: Our cases show some heterogeneity in presentation, with biochemical evidence of diabetic ketoacidosis (DKA) in 4/5 patients, presentation 18–253 days (median 47 days) from ICI commencement, HbA1c 59–78 mmol/mol (median 66 mmol/mol), and c-peptide 0.06–0.77 pmol/mL (median 0.09 pmol/mL). Islet autoantibodies were present in 4/5 cases and high-risk HLA alleles identified in 1/2 tested patients. The findings from our descriptive review support a similar heterogeneity in ICI-DM presentations. Inconsistent diagnostic criteria for ICI-DM were noted with low c-peptide being the most common biochemical presentation. Pancreatic volume is emerging as a useful predictive marker of ICI-DM development. We found no reports of the reversal of ICI-DM with immunosuppression in humans, although recent preclinical studies suggest that this approach is feasible. Conclusions: Diagnostic criteria should include new-onset hyperglycaemia with low paired c-peptide, and may be supported with T1DM-associated autoantibodies and evidence of pancreatic atrophy on imaging. Further research is needed in the realm of predicting ICI-DM and considering the role of immunosuppression as a treatment modality. Full article

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. Full article