MuSK EAMG: Immunological Characterization and Suppression by Induction of Oral Tolerance

Myasthenia gravis (MG) with antibodies to the muscle-specific receptor tyrosine kinase (MuSK) is a distinct sub-group of MG, affecting 5–8% of all MG patients. MuSK, a receptor tyrosine kinase, is expressed at the neuromuscular junctions (NMJs) from the earliest stages of synaptogenesis and plays a crucial role in the development and maintenance of the NMJ. MuSK-MG patients are more severely affected and more refractory to treatments currently used for MG. Most patients require long-term immunosuppression, stressing the need for improved treatments. Ideally, preferred treatments should specifically delete the antigen-specific autoimmune response, without affecting the entire immune system. Mucosal tolerance, induced by oral or nasal administration of an auto-antigen through the mucosal system, resulting in an antigen-specific immunological systemic hyporesponsiveness, might be considered as a treatment of choice for MuSK-MG. In the present study we have characterized several immunological parameters of murine MuSK-EAMG and have employed induction of oral tolerance in mouse MuSK-EAMG, by feeding with a recombinant MuSK protein one week before disease induction. Such a treatment has been shown to attenuate MuSK-EAMG. Both induction and progression of disease were ameliorated following oral treatment with the recombinant MuSK fragment, as indicated by lower clinical scores and lower anti-MuSK antibody titers.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Complement activation as a driver of pathology in myasthenia gravis (MG) has been appreciated for decades. The terminal complement component [membrane attack complex (MAC)] is found at the neuromuscular junctions of patients with MG. Animals with experimental autoimmune MG are dependent predominantly on an active complement system to develop weakness. Mice deficient in intrinsic complement regulatory proteins demonstrate a significant increase in the destruction of the neuromuscular junction. As subtypes of MG have been better defined, it has been appreciated that acetylcholine receptor antibody-positive disease is driven ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
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Source: Journal of Clinical Neuromuscular Disease - Category: Neurology Tags: Review Article Source Type: research
Myasthenia gravis (MG) is a prototypical autoantibody mediated disease. The autoantibodies in MG target structures within the neuromuscular junction (NMJ), thus affecting neuromuscular transmission. The major disease subtypes of autoimmune MG are defined by their antigenic target. The most common target of pathogenic autoantibodies in MG is the nicotinic acetylcholine receptor (AChR), followed by muscle-specific kinase (MuSK) and lipoprotein receptor-related protein 4 (LRP4). MG patients present with similar symptoms independent of the underlying subtype of disease, while the immunopathology is remarkably distinct. Here we...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractThe idea that B  cells participate in immune regulation was initially postulated from observations in animals in the 1970s. It is now established that certain B‐cell populations, known as regulatory B cells, regulate immune reactions in various animal models of autoimmunity, chiefly through the production of in terleukin‐10. Subsequent to these findings in animals, several B‐cell subsets have been identified in human blood that are capable of producing interleukin‐10 when stimulatedex vivo. Although we still do not have direct evidence showing that these interleukin ‐10‐producing B cells ...
Source: Clinical and Experimental Neuroimmunology - Category: Neurology Authors: Tags: REVIEW ARTICLE Source Type: research
Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies predominantly against the acetylcholine receptor (AChR). Specific T cell subsets are required for long-term antibody responses, and cytokines secreted mainly from CD4+ T cells regulate B cell antibody production. The aim of this study was to assess the differences in the cytokine expressions of CD4+ T cells in MG patients with AChR antibodies (AChR-MG) and the effect of immunosuppressive (IS) therapy on cytokine activity and to test these findings also in MG patients without detectable antibodies (SN-MG). Clinically diagnosed AChR-MG and SN-MG patie...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractThe idea that B cells participate in immune regulation was initially postulated from observations in animals in the 1970s. It is now established that certain B ‐cell populations known as regulatory B cells regulate immune reactions in various animal models of autoimmunity, chiefly through the production of interleukin‐10. Subsequent to these findings in animals, several B cell subsets have been identified in human blood that are capable of producing in terleukin‐10 when stimulatedex vivo. Although we still do not have direct evidence showing that these interlukin ‐10 producing B cells regulate autoimmunity ...
Source: Clinical and Experimental Neuroimmunology - Category: Neurology Authors: Tags: REVIEW ARTICLE (INVITED) Source Type: research
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Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
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Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
AbstractThe thymus plays an integral role in immune system regulation, modulating the development, diversity, and selection of T lymphocytes, a critical feature for the prevention of T cell-mediated autoimmunity. Thymoma is a rare tumor of the thymus. Autoimmune diseases and paraneoplastic syndromes such as myasthenia gravis, pure red blood cell aplasia, and systemic lupus erythematosus, although relatively uncommon, have been described in association with thymomas. Rare cases of post-thymectomy autoimmune related diseases, including systemic lupus erythematosus and pure red cell aplasia, have been reported in the literatu...
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
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