scholarly journals Induction of Immunological Tolerance by Oral Anti-CD3

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Andre Pires da Cunha ◽  
Howard L. Weiner
Keyword(s):  
Monoclonal Antibody ◽  
Autoimmune Diseases ◽  
Autoimmune Diabetes ◽  
Immunological Tolerance ◽  
Experimental Models ◽  
Biologically Active ◽  
Chronic Therapy ◽  
Autoimmune Conditions ◽  
Exogenous Antigen ◽  
Immunologic Approach

In recent years, our knowledge about immunoregulation and autoimmunity has significantly advanced, but nontoxic and more effective treatments for different inflammatory and autoimmune diseases are still lacking. Oral tolerance is of unique immunologic importance because it is a continuous natural immunologic event driven by exogenous antigen and is an attractive approach for treatment of these conditions. Parenteral administration of anti-CD3 monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. Orally administered anti-CD3 monoclonal antibody is biologically active in the gut and suppresses experimental models of autoimmune diseases. Orally delivered antibody does not have side effects including cytokine release syndromes, thus oral anti-CD3 antibody is clinically applicable for chronic therapy. Here we review findings that identify a novel and powerful immunologic approach that is widely applicable for the treatment of human autoimmune conditions.

Prevention of autoimmune diabetes with nonactivating anti-CD3 monoclonal antibody

Diabetes ◽  
1992 ◽  
Vol 41 (3) ◽  
pp. 385-391 ◽  
Author(s):  
K. C. Herold ◽  
J. A. Bluestone ◽  
A. G. Montag ◽  
A. Parihar ◽  
A. Wiegner ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Autoimmune Diabetes

Biocompatible Nanovesicular Drug Delivery Systems with Targeting Potential for Autoimmune Diseases

2020 ◽  
Vol 26 (42) ◽  
pp. 5488-5502 ◽  
Author(s):  
Yub Raj Neupane ◽  
Asiya Mahtab ◽  
Lubna Siddiqui ◽  
Archu Singh ◽  
Namrata Gautam ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Drug Delivery Systems ◽  
Drug Carriers ◽  
Immunological Tolerance ◽  
Delivery Systems ◽  
The Body ◽  
Autoimmune Response ◽  
Treatment Modalities

Autoimmune diseases are collectively addressed as chronic conditions initiated by the loss of one’s immunological tolerance, where the body treats its own cells as foreigners or self-antigens. These hay-wired antibodies or immunologically capable cells lead to a variety of disorders like rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis and recently included neurodegenerative diseases like Alzheimer’s, Parkinsonism and testicular cancer triggered T-cells induced autoimmune response in testes and brain. Conventional treatments for autoimmune diseases possess several downsides due to unfavourable pharmacokinetic behaviour of drug, reflected by low bioavailability, rapid clearance, offsite toxicity, restricted targeting ability and poor therapeutic outcomes. Novel nanovesicular drug delivery systems including liposomes, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes and biologically originated exosomes have proved to possess alluring prospects in supporting the combat against autoimmune diseases. These nanovesicles have revitalized available treatment modalities as they are biocompatible, biodegradable, less immunogenic and capable of carrying high drug payloads to deliver both hydrophilic as well as lipophilic drugs to specific sites via passive or active targeting. Due to their unique surface chemistry, they can be decorated with physiological or synthetic ligands to target specific receptors overexpressed in different autoimmune diseases and can even cross the blood-brain barrier. This review presents exhaustive yet concise information on the potential of various nanovesicular systems as drug carriers in improving the overall therapeutic efficiency of the dosage regimen for various autoimmune diseases. The role of endogenous exosomes as biomarkers in the diagnosis and prognosis of autoimmune diseases along with monitoring progress of treatment will also be highlighted.

scholarly journals Polyglandular Autoimmune Syndrome Triggered after CTLA-4 and PD-1L Immunotherapy Treatment

Reports ◽  
2021 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Juan Luis Fernández-Morera ◽  
Alfredo Renilla González ◽  
Carmen Elena Calvo Rodríguez ◽  
Judit Romano-García
Keyword(s):  
Immune Response ◽  
Side Effects ◽  
Autoimmune Diseases ◽  
Autoimmune Diabetes ◽  
Hashimoto Thyroiditis ◽  
Polyglandular Autoimmune Syndrome ◽  
Autoimmune Syndrome ◽  
Previous Diagnosis ◽  
Optimal Approach

Background: CTLA-4 and PD-1L are novel immune checkpoint targets for cancer treatment with specific side effects such as autoimmune diseases. Less frequently, the presence of several autoimmune diseases in the same patient has been described. In this communication, we illustrate the case of a 45-year-old patient with a previous diagnosis of advanced cancer that, after starting treatment with this immunotherapy, developed in the following months autoimmune diabetes, lymphocytic hypophysitis, and a Hashimoto thyroiditis in an abrupt and intense manner that would correspond to an autoimmune polyglandular disease. Discussion: The activation of autoimmunity and associated diseases is increasing in parallel with augmented indication of these immunotherapeutic treatments in cancer patients. A closer follow-up of these patients could be necessary for an optimal approach to this type of pathology. Conclusions: Different autoimmune diseases can converge in the same patient when immunotherapy for cancer is indicated to boost immune response against tumor, caused by altering immune tolerance.

scholarly journals Protection against Autoimmune Diabetes by Silkworm-Produced GFP-Tagged CTB-Insulin Fusion Protein

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Qiaohong Meng ◽  
Wenfeng Wang ◽  
Xiaowen Shi ◽  
Yongfeng Jin ◽  
Yaozhou Zhang
Keyword(s):  
Fusion Protein ◽  
Oral Administration ◽  
Fluorescent Protein ◽  
Autoimmune Diabetes ◽  
Nod Mice ◽  
Treg Cells ◽  
Immunological Tolerance ◽  
Protein Vaccine ◽  
Green Fluorescent

In animals, oral administration of the cholera toxin B (CTB) subunit conjugated to the autoantigen insulin enhances the specific immune-unresponsive state. This is called oral tolerance and is capable of suppressing autoimmune type 1 diabetes (T1D). However, the process by which the CTB-insulin (CTB-INS) protein works as a therapy for T1Din vivoremains unclear. Here, we successfully expressed a green fluorescent protein- (GFP-) tagged CTB-Ins (CTB-Ins-GFP) fusion protein in silkworms in a pentameric form that retained the native ability to activate the mechanism. Oral administration of the CTB-Ins-GFP protein induced special tolerance, delayed the development of diabetic symptoms, and suppressed T1D onset in nonobese diabetic (NOD) mice. Moreover, it increased the numbers of CD4+CD25+Foxp3+T regulatory (Treg) cells in peripheral lymph tissues and affected the biological activity of spleen cells. This study demonstrated that the CTB-Ins-GFP protein produced in silkworms acted as an oral protein vaccine, inducing immunological tolerance involving CD4+CD25+Foxp3+Treg cells in treating T1D.

scholarly journals Research and development of 2-ethyl-6-methyl-3-oxypyridine succinate nano-form for the treatment of epilepsy

2019 ◽  
Vol 10 (4) ◽  
pp. 26-38
Author(s):  
G. G. Avakyan ◽  
T. A. Voronina ◽  
L. N. Nerobkova ◽  
G. N. Avakyan
Keyword(s):  
Status Epilepticus ◽  
Research And Development ◽  
Active Ingredient ◽  
Active Substance ◽  
Drug Transport ◽  
Experimental Models ◽  
Polymer Nanoparticles ◽  
Biologically Active ◽  
Epileptic Focus ◽  
Models Of Epilepsy

The aimis to develop an antiepileptic drug based on polymer nanoparticles with 2-ethyl-6-methyl-3-oxypyridine succinate to facilitate the drug transport through the blood-brain barrier.Materials and methods.The nano-drug was created using the biologically active substance 2-ethyl-6-methyl-3-hydroxypyridine succinate and polybutyl cyanoacrylate (PBCA) nanoparticles. The advantages of this nano-form over the active ingredient of the same drug were studied using experimental models: the maximum electroshock test (MES), the antagonism test with corazol, models with a cobaltinduced epileptic focus and secondary generalized convulsions, and models of status epilepticus.Results.The antiseizure effects of the nanoform on the experimental models of epilepsy are identified.Conclusion.The nano-drug reduces the number of secondary generalized clonic-tonic seizures by 7.8 times; it also reduces 10-fold the animal mortality and diminishes the seizure manifestations that occur in the interictal period of the epileptic status.

scholarly journals Special Issue: Autoimmune Disease Genetics

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1937
Author(s):  
Malgorzata Gabriela Wasniewska ◽  
Artur Bossowski
Keyword(s):  
Autoimmune Disease ◽  
Environmental Factors ◽  
Autoimmune Diseases ◽  
Immunological Tolerance ◽  
Special Issue ◽  
Genetic And Environmental Factors

Autoimmune diseases (ADs) are characterized by a multifactorial etiology, in which genetic and environmental factors are responsible for the loss of immunological tolerance [...]

scholarly journals Long-Term Provision of Acidified Drinking Water Fails to Influence Autoimmune Diabetes and Encephalomyelitis

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Sundararajan Jayaraman ◽  
Arathi Jayaraman
Keyword(s):  
Drinking Water ◽  
Autoimmune Diseases ◽  
Autoimmune Diabetes ◽  
Nod Mice ◽  
Autoimmune Encephalomyelitis ◽  
Gastrointestinal Pathogen ◽  
Onset Of Diabetes ◽  
Partial Blocking

Induction of autoimmune diseases is predisposed by background genetics and influenced by environmental factors including diet and infections. Since consumption of acidified drinking water leads to eradication of gastrointestinal pathogens in animals, we tested whether it may also influence the development of autoimmune diseases. The frequency of spontaneously occurring type 1 diabetes in female NOD mice that were maintained on acidified drinking water by the vendor did not alter after switching to neutral water in our facility. In addition, experimentally induced autoimmune encephalomyelitis was also unaffected by the pH of the drinking water. Interestingly, administration of complete Freund’s adjuvant alone or emulsified with a neuronal peptide to induce neurodegenerative disease during the prediabetic stage completely prevented the onset of diabetes regardless of the pH of the drinking water. However, exposure to microbial products later in life had only a partial blocking effect on diabetes induction, which was also not influenced by the ionic content of the drinking water. Taken together, these data indicate that the onset of autoimmune diseases is not influenced by the gastrointestinal pathogen-depleting treatment, acidified drinking water. Thus, administration of acidic drinking water does not appear to be an option for treating autoimmune diseases.

Characterization of epitopes of seminal plasma antigen stimulating human monoclonal sperm-immobilizing antibodies: a personal review

1989 ◽  
Vol 1 (3) ◽  
pp. 193 ◽  
Author(s):  
S Isojima
Keyword(s):  
Monoclonal Antibody ◽  
Recombinant Dna ◽  
Human Monoclonal Antibody ◽  
Human Sperm ◽  
Biologically Active ◽  
Blood Type ◽  
Type I ◽  
Recombinant Dna Technology ◽  
Sperm Binding ◽  
Carbohydrate Epitopes

In observations made between 1974 and 1984, 40 of 303 women with unexplained sterility (13.2%) showed positive sperm-immobilizing antibodies. Among many kinds of antibodies to human sperm including sperm coating antigens, the biologically active antibodies, such as sperm-immobilizing agglutinating antibodies and blocking antibodies for fertilization, could be relevant to infertility. Harmless sperm-binding antibodies are present even in the sera and cervical mucus of fertile women. Antigens corresponding to monoclonal antibodies (1C4, 2C6, 2E5), which were generated to human sperm coating antigens and indicated strong sperm-immobilizing activities, seemed to have carbohydrate epitopes. The majority of women with sterility of unknown cause appeared to raise sperm-immobilizing antibodies to carbohydrate epitopes of sperm. The stable human-mouse heterohybridoma H6-3C4 secreting monoclonal antibody (IgM, lambda) with extremely high titres of sperm-immobilizing (SI50, 5000 units) and agglutinating (1:1600) activities was successfully established from peripheral lymphocytes of a sterile woman. The chemical structure of an antigen epitope corresponding to human monoclonal antibody H6-3C4 was found to consist of internally repetitive, unbranched N-acetyllactosamine (blood type i antigen). Ejaculated human sperm appeared to be densely covered with sialyl blood type i antigen and sialyl branched internally repetitive N-acetyllactosamine (sialyl blood type I antigen). The antibody-producing V-H and V-L genes of the human hybridoma H6-3C1 were cloned and preserved to stabilize antibody production. Class-switch variants of heavy chain from mu to gamma (IgG1, lambda) in human Mab H6-3C4 were produced by recombinant DNA technology.

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