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Journal Article

Thymic myoid cells and myasthenia gravis.

01 May 1970-American Journal of Pathology (American Society for Investigative Pathology)-Vol. 59, Iss: 2, pp 347-368
About: This article is published in American Journal of Pathology.The article was published on 1970-05-01 and is currently open access. It has received 80 citations till now. The article focuses on the topics: Myasthenia gravis.
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Journal ArticleDOI
01 Jan 1976-Cancer
TL;DR: A clinicopathologic study of 65 patients with thymomas found that syndromes, particularly myasthenia gravis and red cell hypoplasia, affected survival to an equal or greater extent than did the direct effects of the tumors.
Abstract: A clinicopathologic study of 65 patients with thymomas was performed. The most significant prognostic feature of the thymomas was the presence or absence of gross invasion of adjacent tissue. None of 37 patients with non-invasive thymomas died of tumor or had a recurrence. Invasive thymomas resulted in the death of 3 of 17 patients. Two others are alive with unresectable tumor, and one other patient died of myasthenia gravis with recurrent thymoma. The histologic type of thymoma had no value in predicting prognosis. Thirty-five patients had possibly associated syndromes. These syndromes, particularly myasthenia gravis and red cell hypoplasia, affected survival to an equal or greater extent than did the direct effects of the tumors.

257 citations

Journal ArticleDOI
TL;DR: The role of the thymus is still obscure in MG defined by antibodies against the agrin receptor LRP4 and in MG without all of the above autoantibdies (triple sero-negative MG) since these MG subtypes have been described only recently and thymectomy has been their standard treatment.

252 citations

Journal ArticleDOI
TL;DR: Myoid cells were studied by double immunofluorescence in sections of thymus from 47 patients with myasthenia gravis and 15 control subjects, using polyclonal sheep anti–troponin T and monoclonal antibodies to troponin I, striated muscle myosin, and acetylcholine receptor (AChR).
Abstract: Myoid cells were studied by double immunofluorescence in sections of thymus from 47 patients with myasthenia gravis and 15 control subjects, using polyclonal sheep anti-troponin T and monoclonal antibodies to troponin I, striated muscle myosin, and acetylcholine receptor (AChR). The myoid cells were rare and located mainly in the medulla, and most were clearly positive for AChR; labeling was similar with four individual monoclonal antibodies specific for extrajunctional AChR and five that also recognize endplate AChR. They were mostly keratin-positive and consistently HLA-DR-negative. In the myasthenia gravis samples, the myoid cells were similar but largely confined to medullary epithelial areas; AChR labeling was slightly weaker, but otherwise they did not differ noticeably from those of control subjects. A preliminary finding was of even rarer AChR-positive/HLA-DR-positive antigen-presenting (possibly) cells seen in 9 of 9 myasthenia gravis samples and in none of 9 control samples. Although myoid-cell AChR appears antigenically similar to extrajunctional muscle AChR, and must therefore express the epitopes that myasthenics' antibodies recognize, these cells do not appear to be foci of immunological stimulation in myasthenia gravis.

217 citations

Journal ArticleDOI
TL;DR: An updated overview on immunopathogenesis, and derived current and future treatment strategies for MG divided into symptomatic treatments facilitating neuromuscular transmission, antibody-depleting treatments, and immunotherapeutic treatment strategies are provided.
Abstract: Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder of neuromuscular synaptic transmission. The clinical hallmark of MG consists of fluctuating fatigability and weakness affecting ocular, bulbar and (proximal) limb skeletal muscle groups. MG may either occur as an autoimmune disease with distinct immunogenetic characteristics or as a paraneoplastic syndrome associated with tumors of the thymus. Impairment of central thymic and peripheral self-tolerance mechanisms in both cases is thought to favor an autoimmune CD4+ T cell-mediated B cell activation and synthesis of pathogenic high-affinity autoantibodies of either the IgG1 and 3 or IgG4 subclass. These autoantibodies bind to the nicotinic acetylcholine receptor (AchR) itself, or muscle-specific tyrosine-kinase (MuSK), lipoprotein receptor-related protein 4 (LRP4) and agrin involved in clustering of AchRs within the postsynaptic membrane and structural maintenance of the neuromuscular synapse. This results in disturbance of neuromuscular transmission and thus clinical manifestation of the disease. Emphasizing evidence from clinical trials, we provide an updated overview on immunopathogenesis, and derived current and future treatment strategies for MG divided into: (a) symptomatic treatments facilitating neuromuscular transmission, (b) antibody-depleting treatments, and (c) immunotherapeutic treatment strategies.

161 citations


Cites background from "Thymic myoid cells and myasthenia g..."

  • ...Patients with LOMG (Fig....

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  • ...In addition, the number of AIRE positive cells seems to decline as well, however, with no clear difference between LOMG thymuses and age matched controls....

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  • ...The thymus exhibits pathological changes in the majority of patients with AChR antibodies (most patients with OMG, EOMG, LOMG and TAMG; Table 1), which seem to be of central importance for the impairment of central and peripheral tolerance and initiation of immunopathogenesis of MG (Figs....

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  • ...Substantially increased export of naı̈ve T cells has not been observed in LOMG patients at the time of diagnosis [14, 85]....

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  • ...Thymic myoid cells tend to be sparse in LOMG [90, 182], decline with age and can reach a state of near-deficiency between the age of 60 and 70 years, with considerable interpersonal variation [139]....

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Journal ArticleDOI
TL;DR: The strong focus on MG/neuromuscular targets remains unexplained and suggests some biased autoantigen expression, T-cell selection, or autoimmunization within thymomas.
Abstract: Paraneoplastic autoimmune diseases associate occasionally with small cell lung cancers and gynecologic tumors. However, myasthenia gravis (MG) occurs in at least 30% of all patients with thymomas (usually present at MG diagnosis). These epithelial neoplasms almost always have numerous admixed maturing polyclonal T cells (thymocytes). This thymopoiesis-and export of mature CD4(+)T cells-particularly associates with MG, though there are rare/puzzling exceptions in apparently pure epithelial WHO type A thymomas. Other features potentially leading to inefficient self-tolerance induction include defective epithelial expression of the autoimmune regulator (AIRE) gene and/or of major histocompatibility complex class II molecules in thymomas, absence of myoid cells, failure to generate FOXP3(+) regulatory T cells, and genetic polymorphisms affecting T-cell signaling. However, the strong focus on MG/neuromuscular targets remains unexplained and suggests some biased autoantigen expression, T-cell selection, or autoimmunization within thymomas. There must be further clues in the intriguing serological and cellular parallels in some patients with late-onset MG but without thymomas-and in others with AIRE mutations-and in the contrasts with early-onset MG, as discussed here.

159 citations