Involvement In Autoimmune Diseases Research Articles

Cytokines in Follicular Helper T Cell Biology in Physiologic and Pathologic Conditions.

Follicular helper T cells (Tfh) play a crucial role in generating high-affinity antibodies (Abs) and establishing immunological memory. Cytokines, among other functional molecules produced by Tfh, are central to germinal center (GC) reactions. This review focuses on the role of cytokines, including IL-21 and IL-4, in regulating B cell responses within the GC, such as differentiation, affinity maturation, and plasma cell development. Additionally, this review explores the impact of other cytokines like CXCL13, IL-10, IL-9, and IL-2 on GC responses and their potential involvement in autoimmune diseases, allergies, and cancer. This review highlights contributions of Tfh-derived cytokines to both protective immunity and immunopathology across a spectrum of diseases. A deeper understanding of Tfh cytokine biology holds promise for insights into biomedical conditions.

Cardiac magnetic resonance assessment of cardiac involvement in autoimmune diseases.

Cardiac magnetic resonance (CMR) is emerging as the modality of choice to assess early cardiovascular involvement in patients with autoimmune rheumatic diseases (ARDs) that often has a silent presentation and may lead to changes in management. Besides being reproducible and accurate for functional and volumetric assessment, the strength of CMR is its unique ability to perform myocardial tissue characterization that allows the identification of inflammation, edema, and fibrosis. Several CMR biomarkers may provide prognostic information on the severity and progression of cardiovascular involvement in patients with ARDs. In addition, CMR may add value in assessing treatment response and identification of cardiotoxicity related to therapy with immunomodulators that are commonly used to treat these conditions. In this review, we aim to discuss the following objectives: •Illustrate imaging findings of multi-parametric CMR approach in the diagnosis of cardiovascular involvement in various ARDs;•Review the CMR signatures for risk stratification, prognostication, and guiding treatment strategies in ARDs;•Describe the utility of routine and advanced CMR sequences in identifying cardiotoxicity related to immunomodulators and disease-modifying agents in ARDs;•Discuss the limitations of CMR, recent advances, current research gaps, and potential future developments in the field.

Campylobacter jejuni and Postinfectious Autoimmune Diseases: AProof of Concept in Glycobiology.

Glycans, one of the most diverse groups of macromolecules, are ubiquitous constituents of all cells and have many critical functions, including the interaction between microbes and their hosts. One of the best model organisms to study the host-pathogen interaction, the gastrointestinal pathogen Campylobacter jejuni dedicates extensive resources to glycosylation and exhibits a diverse array of surface sugar-coated displays. The first bacterium where N-linked glycosylation was described, C. jejuni can additionally modify proteins by O-linked glycosylation, has extracellular capsular polysaccharides that are important for virulence and represent the major determinant of the Penner serotyping scheme, and has outer membrane lipooligosaccharides that participate in processes such as colonization, survival, inflammation, and immune evasion. In addition to causing gastrointestinal disease and extraintestinal infections, C. jejuni was also linked to postinfectious autoimmune neuropathies, of which Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) are the most extensively characterized ones. These postinfectious autoimmune neuropathies occur when specific bacterial surface lipooligosaccharides mimic gangliosides in the host nervous system. C. jejuni provided the first proof of concept for the involvement of molecular mimicry in the pathogenesis of an autoimmune disease and, also, for the ability of a bacterial polymorphism to shape the clinical presentation of the postinfectious autoimmune neuropathy. The scientific journey that culminated with elucidating the mechanistic details of the C. jejuni-GBS link was the result of contributions from several fields, including microbiology, structural biology, glycobiology, genetics, and immunology and provides an inspiring and important example to interrogate other instances of molecular mimicry and their involvement in autoimmune disease.

The S100A7 nuclear interactors in autoimmune diseases: a coevolutionary study in mammals.

S100A7, a member of the S100A family of Ca2+-binding proteins, is considered a key effector in immune response. In particular, S100A7 dysregulation has been associated with several diseases, including autoimmune disorders. At the nuclear level, S100A7 interacts with several protein-binding partners which are involved in transcriptional regulation and DNA repair. By using the BioGRID and GAAD databases, S100A7 nuclear interactors with a putative involvement in autoimmune diseases were retrieved. We selected fatty acid-binding protein 5 (FABP5), autoimmune regulator (AIRE), cystic fibrosis transmembrane conductance regulator (CFTR), chromodomain helicase DNA-binding protein 4 (CHD4), epidermal growth factor receptor (EGFR), estrogen receptor 1 (ESR1), histone deacetylase 2 (HDAC2), v-myc avian myelocytomatosis viral oncogene homolog (MYC), protection of telomeres protein 1 (POT1), telomeric repeat-binding factor (NIMA-interacting) 1 (TERF1), telomeric repeat-binding factor 2 (TERF2), and Zic family member 1 (ZIC1). Linear correlation coefficients between interprotein distances were calculated with MirrorTree. Coevolution clusters were also identified with the use of a recent version of the Blocks in Sequences (BIS2) algorithm implemented in the BIS2Analyzer web server. Analysis of pair positions identified interprotein coevolving clusters between S100A7 and the binding partners CFTR and TERF1. Such findings could guide further analysis to better elucidate the function of S100A7 and its binding partners and to design drugs targeting for these molecules in autoimmune diseases.

Right ventriculoarterial coupling as a marker of subclinical myocardial damage in rheumatoid arthritis

Abstract Funding Acknowledgements Type of funding sources: None. Background The lung involvement in autoimmune diseases has been described previously. Currently the incidence of pulmonary hypertension in patients with rheumatoid arthritis (RA) ranges from 1-25%. Right ventriculoarterial coupling (RVAC) is altered early before presenting right ventricular dysfunction and pulmonary hypertension, its measurement in patients with RA has been barely studied. Objectives To determine if there is a difference in RVAC in patients with RA. Analyze if there are differences in patients with normal vs abnormal right RVAC. To investigate if there is an association in patients with RA to present abnormal RVAC. Methods A single-center, analytical, cross-sectional, observational study was performed. Patients with diagnosis of RA were included according to the ACR / EULAR 2010 classification criteria, without any other comorbidity. An ACUSON SC2000 echocardiogram was used. Patients were compared with healthy controls matched by age and gender. The clinical, laboratory and echocardiographic variables were contrasted. Among the echocardiographic variables, the left ventricular ejection fraction, the left ventricular volume index, the left atrial volume index, right ventricular diastolic area, right ventricular fractional area change (RV FAC), right atrial volume, pulmonary artery systolic pressure (PASP), right ventricular free wall longitudinal strain (RVFWLS) and right atrial global longitudinal strain (RAGLS). The RVAC was determined with the RVFWLS / PSAP ratio. A RVAC less than 0.8 was classified as abnormal. The quantitative variables were contrasted with Student"s t-test or Mann-Whitney"s u test, according to the normality of the variables; qualitative variables were compared with x2. The association with an abnormal RVAC was determined with univariate and multivariate analysis. Results Thirty-four patients were included in each group. Among the echocardiographic variables, it was found that patients with RA had a greater right ventricular diastolic area and the PASP; while the RV FAC, the RVFWLS and the RVAC were lower. 68% of the RA patients had an abnormal RVAC, and C-reactive protein (CRP) levels were higher in patients with an abnormal RVAC.  In the multivariate analysis, we found that patients with RA and CRP levels were independently associated to an abnormal RVAC. Conclusion The right ventricular subclinical myocardial damage, determined by the RVAC, is present in patients with rheumatoid arthritis. CRP levels and rheumatoid arthritis were associated with an abnormal ventriculoarterial coupling. Abstract Table 1  Abstract Table 2

Lung fibrosis in autoimmune diseases and hypersensitivity: how to separate these from idiopathic pulmonary fibrosis

Lung involvement in autoimmune diseases (AID) is uncommon, but may precede other organ manifestations. A diagnostic problem is chronicity presenting with lung fibrosis. A new category of interstitial pneumonia with autoimmune features for patients with clinical symptoms of AID and presenting with usual interstitial pneumonia (UIP) enables antifibrotic treatment for these patients. Hypersensitivity pneumonia (HP) and other forms of lung fibrosis were not included into this category. As these diseases based on adverse immune reactions often present with unspecific clinical symptoms, a specified pathological diagnosis will assist the clinical evaluation. We aimed to establish etiology-relevant differences of patterns associated with AID or HP combined with lung fibrosis. We retrospectively evaluated 51 cases of AID, and 29 cases of HP with lung fibrosis, and compared these to 24 cases of idiopathic pulmonary fibrosis (UIP/IPF). Subacute AID and HP most often presented with organizing pneumonia (OP), whereas chronicity was associated with UIP. Unspecified fibrosis was seen in a few cases, whereas NSIP pattern was rare. In 9 cases, the underlying etiology could not be defined. Statistically significant features differentiating chronic AID or HP from UIP/IPF are lymphocytic infiltrations into myofibroblastic/fibroblastic foci. Other features significantly associated with AID and HP were granulomas, isolated Langhans giant cells, and protein deposits, but seen in only a minority of cases. A combination of UIP with one of these features enabled a specific etiology-based diagnosis. Besides the antifibrotic drug regimen, additional therapies might be considered.

Rheumatoid Arthritis: The Problems Beyond the Joints

An autoimmune disease is defined as a clinical syndrome resulted from instigation of both T cell and B cell or individually, in the absence of any present infection or any sort of distinguishable cause. Rheumatoid arthritis is chronic and systemic autoimmune response to multiple joints with unknown etiology, progressive disability, systemic complications, early death and high socioeconomic costs. Rheumatoid arthritis is characterised by hyperplastic synovium, production of cytokines, chemokines, autoantibodies like rheumatoid factor (Rf) and anticitrullinated protein antibody (ACPA), osteoclastogenisis, angiogenisis and systemic consequences like cardiovascular, pulmonary, psychological and skeletal disorders. Cytokines a diverse group of polypeptides, play critical role in the pathogenesis of Rheumatoid arthritis. Their involvement in autoimmune disease is a rapidly growing area of biological and clinical research. Pharmacotherapy should target the balance between the pro and anti-inflammatory cytokines that is believe to be the central dogma in the pathogenesis of rheumatoid arthritis.[1] Elevated sympathetic and parasympathetic nervous system activities are expected to occur as a consequence of inflammatory stress.[2] For this we need to explore new treatment modalities to find the answers for unresolved etiology of autoimmune disease and to provide a quality of life to the patients suffering from rheumatoid arthritis. Read More ...

Role of Myeloid-derived suppressor cell (MDSC) in autoimmunity and its potential as a therapeutic target

Myeloid suppressor cells (MDSCs) are an important class of immune-regulating cells that can suppress T cell function. Most of our knowledge about the function of MDSC comes from studies of cancer models. Recent studies, however, have greatly contributed to the description of MDSC involvement in autoimmune diseases. They are known as a cell population that may negatively affect immune responses by regulating the function of CD4+ and CD8+ cells, which makes them an attractive target for autoimmune diseases therapy. However, many questions about MDSC activation, differentiation, and inhibitory functions remain unanswered. In this study, we have summarized the role of MDSCs in various autoimmune diseases, and the potential of targeting them for therapeutic benefits has been discussed.

A1 and A2A adenosine receptors play a protective role to reduce prevalence of autoimmunity following tissue damage.

Adenosine is a potent modulator that has a tremendous effect on the immune system. Adenosine affects T cell activity, and is necessary in maintaining the T helper/regulatory T cell (Treg ) ratio. Adenosine signalling is also involved in activating neutrophils and the formation of neutrophil extracellular traps (NETs), which has been linked to autoimmune disorders. Therefore, adenosine, through its receptors, is extremely important in maintaining homeostasis and involved in the development of autoimmune diseases. In this study, we aim to evaluate the role of adenosine A1 and A2A receptors in involvement of autoimmune diseases. We studied adenosine regulation by NETosis in vitro, and used two murine models of autoimmune diseases: type I diabetes mellitus (T1DM) induced by low-dose streptozotocin and pristane-induced systemic lupus erythematosus (SLE). We have found that A1 R enhances and A2A R suppresses NETosis. In addition, in both models, A1 R-knock-out (KO) mice were predisposed to the development of autoimmunity. In the SLE model in wild-type (WT) mice we observed a decline of A1 R mRNA levels 6h after pristane injection that was parallel to lymphocyte reduction. Following pristane, 43% of A1 R-KO mice suffered from lupus-like disease while WT mice remained without any sign of disease at 36weeks. In WT mice, at 10days A2A R mRNA levels were significantly higher compared to A1R-KO mice. Similar to SLE, in the T1DM model the presence of A1 R and A2A R was protective. Our data suggest that, in autoimmune diseases, the acute elimination of lymphocytes and reduction of DNA release due to NETosis depends upon A1 R desensitization and long-term suppression of A2A R.

JOINT PAINS AND A RACING HEART- VENTRICULAR TACHYCARDIA AS AN INITIAL PRESENTATION OF UNDERLYING SCLERODERMA RELATED AUTOIMMUNE MYOCARDITIS

Background Myocardial involvement, especially with ventricular tachycardia as an initial presentation, is uncommon in scleroderma. Case A 56 year-old male presented with exertional dyspnea, palpitations and bilateral hand arthralgias. Physical examination showed regular tachycardia, no jugular venous distension, clear lungs, no cardiac murmurs and skin thickening of digits of both hands. Electrocardiogram showed sinus tachycardia. CXR showed bibasilar interstitial prominence. Laboratory studies showed troponin 0.15 ng/mL, normal BNP, WBC 2.27 K/uL and negative SARS-CoV2 PCR. 24 hours after admission, he developed sustained monomorphic ventricular tachycardia and hypotension, responding to amiodarone, lidocaine and IV fluids. Cardiac catheterization showed no CAD. CT chest showed no pulmonary embolism but lower lobe reticular, ground-glass opacities. Echocardiogram revealed moderate LV systolic dysfunction and inferolateral hypokinesis. Cardiac MRI showed similar wall motion abnormalities and diffuse sub-epicardial myocardial scar. Decision-making The patient was arrhythmia free on sotalol and carvedilol. Transbronchial lung biopsy was negative for sarcoidosis. Corticosteroids were started empirically. A defibrillator was placed for secondary prevention. Rheumatoid factor was negative, anti-CCP weakly positive (25 u), ANA >1:320, ACE levels normal, ESR 69 mm/h, CRP 15.2. He was diagnosed with scleroderma and started on Cellcept. Three months after hospitalization, he is free of ventricular arrhythmias and arthralgias are improved Conclusion Cardiac involvement in autoimmune disease can lead to rhythm abnormalities and sudden cardiac death (1);it is often missed in scleroderma and if found, diagnosis is usually made more than one year after rheumatologic diagnosis (2). Autoimmune myocarditis (AM) is associated with poor prognosis (3). Early initiation of anti-arrhythmic agents, medical optimization for LV dysfunction, ICD placement and corticosteroids/immunosuppressants have benefited our patient. Early recognition of AM and multidisciplinary approach are imperative for successful outcome.

The outcomes of fetal cell microchimerism in the mother

The presence of small quantities of genetically heterogeneous cells in an organism is known as microchimerism. Fetal microchimerism is the presence of small quantities of fetal cells in the maternal system during and after pregnancy. Since these cells are semi-allogeneic in the mother's body, they have an impact on the mother's health. Recent studies suggest contradictory outcomes. Some suggest an involvement in autoimmune diseases and cancer. Others suggest involvement in tissue repair and wound healing. Fetal cells have been detected in maternal organs decades after pregnancy. It was found that these cells participate in the healing process post a chronic injury. In other cases, these cells initiate an immune response which may lead to the development of autoimmune diseases. Further, studies show that fetal cells have been discovered in the tumor microenvironment, either aiding in cancer development or eradicating the cancer cells. Here, I review the different outcomes that can occur in the female body because of fetal cell microchimerism. I discuss the presence of fetal cells in maternal organs such as the heart and the central nervous system organs and their involvement in disease development and tissue repair in the mother.

Usefulness of Myocardial Strain and Twist for Early Detection of Myocardial Dysfunction in Patients With Autoimmune Diseases

Cardiac involvement in autoimmune diseases (AD) is common but underdiagnosed due to a lack of sensitive imaging methods. We aim to evaluate the characteristics of left ventricular (LV) systolic dysfunction in patients with AD using deformational parameters from 2-dimensional speckle-tracking echocardiography (STE). We retrospectively enrolled 86 AD patients and 71 healthy controls. All subjects underwent transthoracic echocardiography and STE to analyze LV strain and twist. A twist-radial displacement loop was constructed to investigate the relation between LV contractility and dimension. In AD patients, 68 had preserved LV ejection fraction (EF ≥ 50%), and 18 had reduced LVEF (EF < 50%). The patients with preserved LVEF exhibited significantly lower values of global longitudinal, circumferential, and radial strain than controls (-19.11 ± 4.18 vs -21.49 ± 2.53%, -25.17 ± 5.04% vs -27.37 ± 2.87%, 17.68 ± 5.69% vs 21.17 ± 6.44%, respectively; all p <0.01) and a marked attenuation in peak twist (14.24 ± 5.57 vs 18.10 ± 5.97, p <0.01) attributed to impaired apical rotation (9.03 ± 5.17 vs 12.79 ± 5.99, p <0.01). AD patients were more likely to present with abnormal loop types with flat ascending slope and delayed peak twist time. In conclusion, abnormal strain and twist precede deterioration in LVEF, suggesting early myocardial involvement in AD. STE can be used as a good alternative for early detection of myocardial dysfunction in AD patients.

Women with silicone breast implants and autoimmune inflammatory syndrome induced by adjuvants: description of three patients and a critical review of the literature

Silicone has been widely used in the manufacture of medical implants. It is well tolerated in most cases. However, in this paper we report the cases of three women who developed autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome), namely with silicone breast implants. The symptoms in these cases include arthralgia, arthritis, myalgia, sleep disturbances, the appearance of autoantibodies, miscarriage, Raynaud's phenomenon, and involvement of autoimmune diseases (scleroderma and undifferentiated connective tissue diseases). In one patient, breast implants were removed, but no improvement was seen after the removal. The remaining two patients received the updated information about their condition, and they decided not to remove the implants. In conclusion, earlier reports that silicone is biologically relatively inert have recently been challenged with the description of ASIA syndrome.

(1367) - Does Endomyocardial Biopsy (EMB) Contribute to Management of Patients with Myocardial Involvement in Autoimmune Disease?

(1367) - Does Endomyocardial Biopsy (EMB) Contribute to Management of Patients with Myocardial Involvement in Autoimmune Disease?

Extracellular Actin in Health and Disease.

This review considers the functions of extracellular actin - cell surface bound, associated with extracellular matrix, or freely circulating. The role of this protein in different pathological processes is analyzed: its toxic effects and involvement in autoimmune diseases as an autoantigen. The extracellular actin clearance system and its role in protection against the negative effects of actin are characterized. Levels of free-circulating actin, anti-actin immunoglobulins, and components of the actin clearance system as prognostic biomarkers for different diseases are reviewed. Experimental approaches to protection against excessive amounts of free-circulating F-actin are discussed.

Blockade of Glutamine Synthetase Enhances Inflammatory Response in Microglial Cells.

Microglial cells are brain-resident macrophages engaged in surveillance and maintained in a constant state of relative inactivity. However, their involvement in autoimmune diseases indicates that in pathological conditions microglia gain an inflammatory phenotype. The mechanisms underlying this change in the microglial phenotype are still unclear. Since metabolism is an important modulator of immune cell function, we focused our attention on glutamine synthetase (GS), a modulator of the response to lipopolysaccharide (LPS) activation in other cell types, which is expressed by microglia. GS inhibition enhances release of inflammatory mediators of LPS-activated microglia in vitro, leading to perturbation of the redox balance and decreased viability of cocultured neurons. GS inhibition also decreases insulin-mediated glucose uptake in microglia. In vivo, microglia-specific GS ablation enhances expression of inflammatory markers upon LPS treatment. In the spinal cords from experimental autoimmune encephalomyelitis (EAE), GS expression levels and glutamine/glutamate ratios are reduced. Recently, metabolism has been highlighted as mediator of immune cell function through the discovery of mechanisms that (behind these metabolic changes) modulate the inflammatory response. The present study shows for the first time a metabolic mechanism mediating microglial response to a proinflammatory stimulus, pointing to GS activity as a master modulator of immune cell function and thus unraveling a potential therapeutic target. Our study highlights a new role of GS in modulating immune response in microglia, providing insights into the pathogenic mechanisms associated with inflammation and new strategies of therapeutic intervention. Antioxid. Redox Signal. 26, 351-363.

[The Role of Bronchoalveolar Lavage in the Diagnosis of Idiopathic Pulmonary Fibrosis: An Investigation of the Relevance of the Protein Content].

Although bronchoalveolar lavage (BAL) is often used in the diagnosis of interstitial lung diseases (ILDs), its importance in investigating, in particular, idiopathic pulmonary fibrosis (IPF) is controversial. The cell distributions in the BAL are taken into account in the clinical routine, non-cellular characteristics of the BAL play no role.Using mathematical modeling of data, the present work investigated the extent to which BAL features enable drawing conclusions about the underlying ILK or help exclude IPF. Included in the calculation are cellular findings of the BAL, in addition the protein and albumin content of the BAL, the nicotine history (pack years), and spirometry (FEV1, IVC).Using linear discriminant analysis and creating classification trees, the relevance of the characteristics of 806 patients with ILK was examined (183 IPF, 191 cryptogenic organizing pneumonia, 147 lung involvement in autoimmune disease, 97 respiratory bronchiolitis interstitial lung disease, 118 extrinsic allergic alveolitis, 41 lymphocytic interstitial pneumonia (LIP), 23 non-specific interstitial pneumonia (NSIP), 88 controls).There was a close positive relationship between protein levels and lymphocytes in the group as a whole. No such correlations were seen in IPF and NSIP. Albumin was closely correlated with the protein content in all groups.The lymphocytes are best suited to distinguish between different ILDs. Yet, a reliable calculation of the ILD is not possible on the basis of the investigated factors, the classification error ranged from 23.5 % (IPF) to 100 % (LIP, NSIP).Constellations that likely (> 99 %) speak against an IPF are lymphocytosis > 34 % or protein content > 347 mg/l. The same applies to the constellation: lymphocytes > 25 % together with protein > 250 mg/l.In ILD, BAL findings can narrow the diagnosis, but they are seldom diagnostic. BAL can make an important contribution to excluding of IPF.

At the Bench: Neutrophil extracellular traps (NETs) highlight novel aspects of innate immune system involvement in autoimmune diseases

The putative role of neutrophils in host defense against pathogens is a well-recognized aspect of neutrophil function. The discovery of neutrophil extracellular traps has expanded the known range of neutrophil defense mechanisms and catalyzed a discipline of research focused upon ways in which neutrophils can shape the immunologic landscape of certain autoimmune diseases, including systemic lupus erythematosus. Enhanced neutrophil extracellular trap formation and impaired neutrophil extracellular trap clearance may contribute to immunogenicity in systemic lupus erythematosus and other autoimmune diseases by promoting the externalization of modified autoantigens, inducing synthesis of type I IFNs, stimulating the inflammasome, and activating both the classic and alternative pathways of the complement system. Vasculopathy is a central feature of many autoimmune diseases, and neutrophil extracellular traps may contribute directly to endothelial cell dysfunction, atherosclerotic plaque burden, and thrombosis. The elucidation of the subcellular events of neutrophil extracellular trap formation may generate novel, therapeutic strategies that target the innate immune system in autoimmune and vascular diseases.

The current role and therapeutic targets of vitamin D in gastrointestinal inflammation and cancer.

Vitamin D, beyond its classical roles in the regulation of calcium and phosphorus homeostasis and bone metabolism, has been implicated in multiple pathological processes, including progression from inflammation to cancer development and also involvement in autoimmune diseases as well as cardiovascular disorders. In this review, we shall discuss the different roles of vitamin D and its therapeutic targets in different gastrointestinal diseases, focusing on colorectal cancer (CRC) and inflammatory bowel disease (IBD). To this end, vitamin D deficiency has been identified as a risk factor of CRC. On the other hand the active metabolite of vitamin D, 1, 25- dihydroxyvitamin D3 (1, 25(OH)2D3) has multiple anti-cancerous benefits including inhibition of proliferation, induction of apoptosis, promotion of differentiation and suppression of angiogenesis in tumors. In IBD, vitamin D is involved in the pathogenic process through the normalization of immune responses in the colon. With these experimental findings, well-designed and large-scale clinical trials are warranted to further define the therapeutic action of vitamin D in the prevention and/or treatment of IBD and further on CRC in humans.

Contribution of autoallergy to the pathogenesis in the NOD mice

The immunoglobulin isotype IgE is commonly associated with allergy. However, its involvement in autoimmune disease in general, and Type 1 diabetes (T1D) in particular, is still not completely clarified, nonetheless IgE has been observed in patients with T1D. In this article, we aimed to elucidate the contribution of IgE in the pathogenesis of the disease in a spontaneous model for T1D, i.e. the NOD mouse. We observed increased levels of IgE in splenic, lymph node and peripheral blood B cells in the NOD mice compared to the control C57BL/6 (B6) mice. No correlation was found between the IgE levels on B cells and those in the sera of these mice, indicating a B cell intrinsic property mediating IgE capture in NOD. Functionally, the B cells from NOD were similar to B6 in rescuing the IgE-mediated immune response via the low affinity receptor CD23 in a transgenic adoptive transfer system. However, the involvement of IgE in diabetes development was clearly demonstrated, as treatment with anti-IgE antibodies delayed the incidence of the diabetes in the NOD mice compared to the PBS treated group. Pancreas sections from a 13-week-old NOD revealed the presence of tertiary lymphoid structures with T cells, B cells, germinal centers and IgE suggesting the presence of autoantigen specific IgE. Our study provides an insight to the commonly overlooked immunoglobulin IgE and its potential role in autoimmunity.