Antigen-specific immunotherapies in type 1 diabetes

Zhang, Xuejiao; Dong, Ying; Liu, Dianyuan; Liu, Yang; Xu, Jiayi; Wang, Qing

doi:10.1016/j.jtemb.2022.127040

Cited by 15 publications

(11 citation statements)

References 152 publications

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“…Many antigen-specific therapeutic strategies have been tested, as summarized in Table 2 . Strategies to promote immune tolerance against T1D autoantigens include GAD peptide immunization, oral insulin administration, and proinsulin-encoding plasmid DNA immunization [ 152 ], as reviewed by Zhang et al [ 149 ]. In a study of autoantibody-positive relatives of patients with T1D, oral insulin compared to a placebo did not delay or prevent the development of T1D over 2.7 years [ 150 ].…”

Section: Antigen-specific Therapy In T1dmentioning

confidence: 99%

“…Herold et al postulate that these regulatory T cells may be induced by IL-10 producing B cells that repopulate after rituximab cessation [139]. GAD peptide immunization GAD-specific B and T lymphocytes Variable impact on beta-cell function [149] Oral insulin Insulin-specific B and T lymphocytes Variable immune responses [149][150][151] Proinsulin-encoding plasmid DNA immunization (Pro)insulin-specific T lymphocytes Preservation of beta-cell function in adult T1D individuals over 15-week follow-up period [152] In Mouse mAb123 Insulin-bound B lymphocytes Protects from T1D [80] Soluble antigen array Autoantigen-specific B and T lymphocytes Protects from T1D [153,154] Healthy polyclonal IgM Insulin-binding B lymphocytes Reverses T1D [155] Insulin-CD22L conjugate Insulin-binding B lymphocyte Reduced anti-insulin B cell proliferation with anti-CD40 stimulation in vitro [156] AKS-107 Insulin-binding B lymphocytes Protects from T1D [157] Unsurprisingly, rituximab treatment depleted protective antibody responses to vaccination against a neoantigen bacteriophage phiX174 administered to T1D individuals during the time of B cell depletion [158]. Antibody response to hepatitis A, tetanus, and diphtheria vaccination during the time of B cell recovery reached levels of clinical response but was still impaired compared to placebo-treated T1D individuals [158], highlighting concerns related to dampened infection and vaccination responses.…”

Section: B-cell-targeted Immunotherapy In Human T1dmentioning

confidence: 99%

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Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes

Bass,

Bonami

2024

Antibodies

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Islet autoantibodies predict type 1 diabetes (T1D) but can be transient in murine and human T1D and are not thought to be directly pathogenic. Rather, these autoantibodies signal B cell activity as antigen-presenting cells (APCs) that present islet autoantigen to diabetogenic T cells to promote T1D pathogenesis. Disrupting B cell APC function prevents T1D in mouse models and has shown promise in clinical trials. Autoantigen-specific B cells thus hold potential as sophisticated T1D biomarkers and therapeutic targets. B cell receptor (BCR) somatic hypermutation is a mechanism by which B cells increase affinity for islet autoantigen. High-affinity B and T cell responses are selected in protective immune responses, but immune tolerance mechanisms are known to censor highly autoreactive clones in autoimmunity, including T1D. Thus, different selection rules often apply to autoimmune disease settings (as opposed to protective host immunity), where different autoantigen affinity ceilings are tolerated based on variations in host genetics and environment. This review will explore what is currently known regarding B cell signaling, selection, and interaction with T cells to promote T1D pathogenesis.

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Section: Antigen-specific Therapy In T1dmentioning

confidence: 99%

Section: B-cell-targeted Immunotherapy In Human T1dmentioning

confidence: 99%

Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes

Bass,

Bonami

2024

Antibodies

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“…Using AAgs as biomarkers has been shown as pivotal for prediction prior to disease onset and diagnosis–autoantibodies against β-cell proteins and peptides are now used almost routinely to predict the disease and help diagnose of T1DM [ 44 ]. Their recognition as biomarkers of pre-symptomatic disease has led to proposals for early type 1 diabetes staging using a range of autoantibodies for diagnosis–a concept that is starting to make its way into practice [ 45 , 46 , 47 ]—and it also important for the development of autoantigen-specific tolerance induction immunotherapy [ 16 ], such as for example targeting the ZnT8 antigen [ 48 ].…”

Section: Type 1 Diabetes Mellitusmentioning

confidence: 99%

Type 1 Diabetes Mellitus: A Review on Advances and Challenges in Creating Insulin Producing Devices

et al. 2023

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Type 1 diabetes mellitus (T1DM) is the most common autoimmune chronic disease in young patients. It is caused by the destruction of pancreatic endocrine β-cells that produce insulin in specific areas of the pancreas, known as islets of Langerhans. As a result, the body becomes insulin deficient and hyperglycemic. Complications associated with diabetes are life-threatening and the current standard of care for T1DM consists still of insulin injections. Lifesaving, exogenous insulin replacement is a chronic and costly burden of care for diabetic patients. Alternative therapeutic options have been the focus in these fields. Advances in molecular biology technologies and in microfabrication have enabled promising new therapeutic options. For example, islet transplantation has emerged as an effective treatment to restore the normal regulation of blood glucose in patients with T1DM. However, this technique has been hampered by obstacles, such as limited islet availability, extensive islet apoptosis, and poor islet vascular engraftment. Many of these unsolved issues need to be addressed before a potential cure for T1DM can be a possibility. New technologies like organ-on-a-chip platforms (OoC), multiplexed assessment tools and emergent stem cell approaches promise to enhance therapeutic outcomes. This review will introduce the disorder of type 1 diabetes mellitus, an overview of advances and challenges in the areas of microfluidic devices, monitoring tools, and prominent use of stem cells, and how they can be linked together to create a viable model for the T1DM treatment. Microfluidic devices like OoC platforms can establish a crucial platform for pathophysiological and pharmacological studies as they recreate the pancreatic environment. Stem cell use opens the possibility to hypothetically generate a limitless number of functional pancreatic cells. Additionally, the integration of stem cells into OoC models may allow personalized or patient-specific therapies.

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“…No exact cause has been found to justify how the disease occurs. Hereditary, genetic, or environmental factors predispose to T1D 3,5 . In the past few decades, the most common treatment for T1D has been utilizing islet cells or islets of Langerhans, eliminating patients' need to receive insulin.…”

Section: Introductionmentioning

confidence: 99%

“…Hereditary, genetic, or environmental factors predispose to T1D. 3,5 In the past few decades, the most common treatment for T1D has been utilizing islet cells or islets of Langerhans, eliminating patients' need to receive insulin. The limitation of therapy was due to the risk of rejection, the shortage of donors, and the possibility of thrombosis, diabetes, and cancer through some immunosuppressive drugs.…”

Section: Introductionmentioning

confidence: 99%

Generation of glucose sensitive insulin‐secreting cells from human induced pluripotent stem cells on optimized polyethersulfone hybrid nanofibrous scaffold

et al. 2022

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Background: In the realm of diabetes treatment, various strategies have been tried, including islet transplantation and common drug therapies, but the limitations of these procedures and lack of responsive to the high number of patients have prompted researchers to develop a new method. In recent decades, the use of stem cells and three-dimonsional (3D) scaffold to produce insulin-secreting cells is one of the most promising new approaches. Meanwhile, human-induced pluripotent stem cells (iPSCs) propose due to advantages such as autologousness and high pluripotency in cell therapy. This study aimed to evaluate the differentiation of iPSCs into pancreatic islet insuli-producing cells (IPCs) on Silk/ PES (polyethersulfone) nanofibers as a 3D scaffold and compare it with a twodimonsional (2D) cultured group.Methods: Investigating the functional, morphological, molecular, and cellular characteristics of differentiated iPSCs on control cultures (without differentiation medium), 2D and 3D were measured by various methods such as electron microscopy, Q-PCR, immunofluorescence, western blot, and ELISA.Results: This investigation revealed that differentiated cells on the 3D Silk/PES scaffold expressed pancreatic specific-markers such as insulin and pdx1 at higher levels than the control and 2D groups, with a significant difference between the two groups. All results of Q-PCR, immunocytochemistry, and western blot showed that IPCs in the silk/PES 3D group was more efficient than in the 2D group. In the face of these cases, the release of insulin and C-peptide in response to several concentrations of glucose in the 3D group was significantly higher than in the 2D culture. Conclusion:Finally, our findings displayed that optimized Silk/PES 3D scaffolds can enhance the differentiation of IPCs from iPSCs compared to the 2D culture group.

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Antigen-specific immunotherapies in type 1 diabetes

Cited by 15 publications

References 152 publications

Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes

Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes

Type 1 Diabetes Mellitus: A Review on Advances and Challenges in Creating Insulin Producing Devices

Generation of glucose sensitive insulin‐secreting cells from human induced pluripotent stem cells on optimized polyethersulfone hybrid nanofibrous scaffold

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