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Sample records for autoimmune myasthenia gravis

  1. Autoimmune myasthenia gravis.

    PubMed

    Jayawant, Sandeep; Parr, Jeremy; Vincent, Angela

    2013-01-01

    Myasthenia gravis in children can be generalized or ocular, and associated with antibodies to acetylcholine receptors or muscle-specific kinase, but it can be negative for those antibodies (seronegative). It needs to be distinguished from congenital myasthenic syndromes and other neuromuscular diseases. In the perinatal period, transient neonatal myasthenia and arthrogryposis multiplex congenita, due to maternal antibodies, need to be considered. Juvenile myasthenia is similar in presentation and treatment to that in adults. Here we present guidelines for recognition, diagnosis, and treatment. PMID:23622368

  2. Myasthenia Gravis

    MedlinePlus

    Myasthenia gravis is a disease that causes weakness in the muscles under your control. It happens because ... problem in communication between your nerves and muscles. Myasthenia gravis is an autoimmune disease. Your body's own ...

  3. Autoimmune myasthenia gravis, immunotherapy and thymectomy in children.

    PubMed

    Ware, Tyson L; Ryan, Monique M; Kornberg, Andrew J

    2012-02-01

    Autoimmune myasthenia gravis is a rare condition in children. Identifying antibodies directed against the acetylcholine receptor is helpful in making the diagnosis. However, seronegative cases do exist and need to be distinguished from congenital forms of myasthenia. There is little published experience to inform the judicious management of autoimmune myasthenia gravis in children. In this article, we report our experience in the management of 12 cases of autoimmune myasthenia gravis in children in the modern era of medical immunotherapy and thymectomy. PMID:21911294

  4. [Myasthenia gravis].

    PubMed

    Schodrowski, J; Seipelt, M; Adibi-Sedeh, I; Eienbröker, C; Tackenberg, B

    2016-04-01

    Myasthenia gravis is an autoimmune disease, which leads to load-dependent weakness of voluntary skeletal muscles with recovery of function after resting. The disease is caused by autoantibodies directed against the postsynaptic nicotinic acetylcholine receptors (AChR) leading to a reduction of neuromuscular transmission. Muscles and nerves are not affected. Disorders of the thymus play a role in the pathogenesis of AChR antibody-positive myasthenia. The clinical symptoms include exercise-induced fatigue either of the ocular muscles alone (ocular myasthenia) or striated skeletal muscle and the ocular, facial and bulbar musculature (generalized myasthenia). Treatment of myasthenia gravis involves administration of acetylcholine esterase inhibitors and immunosuppressive drugs. A myasthenic crisis is characterized by life-threatening complications with severe weakness, swallowing difficulties and respiratory failure, which requires intensive care treatment. PMID:27000188

  5. Complicating autoimmune diseases in myasthenia gravis: a review

    PubMed Central

    Nacu, Aliona; Andersen, Jintana Bunpan; Lisnic, Vitalie; Owe, Jone Furlund; Gilhus, Nils Erik

    2015-01-01

    Abstract Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis. PMID:25915571

  6. Myasthenia gravis, a model of organ-specific autoimmune disease.

    PubMed

    Berrih-Aknin, S

    1995-04-01

    Myasthenia gravis (MG) is a neuromuscular disorder of autoimmune origin. Most patients have antibodies directed against the acetylcholine receptor (AChR) that interfere with neuromuscular transmission. MG is a model of organ-specific autoimmune disease in which the autoantigen, AChR, is well characterized. However, several questions remain unanswered. Why is AChR, which is present in the thymus, not tolerized? Why does the anti-AChR antibody titre not correlate with clinical manifestations, and why do some patients not have such antibodies? What genetic elements are involved in disease susceptibility? How is the expression of AChR regulated after its attack by autoantibodies? Could MG patients benefit from new immunomodulatory treatments? At the IVth EuroMyasthenia meeting, held in Versailles in April 1994, almost 200 researchers and physicians met to discuss the pathophysiology and treatment of myasthenia gravis and to provide answers to some of these questions. The sessions covered immunological, genetic and clinical aspects of MG. PMID:7612144

  7. Treatment of passively transferred experimental autoimmune myasthenia gravis using papain

    PubMed Central

    Poulas, K; Tsouloufis, T; Tzartos, S J

    2000-01-01

    Antibody-mediated acetylcholine receptor (AChR) loss at the neuromuscular junction, the main cause of the symptoms of myasthenia gravis, is induced by bivalent or multivalent antibodies. Passive transfer of experimental autoimmune myasthenia gravis (EAMG) can be induced very efficiently in rats by administration of intact MoAbs directed against the main immunogenic region (MIR) of the AChR, but not by their monovalent Fab fragments. We tested whether papain, which has been used therapeutically in autoimmune and other diseases, is capable of preventing EAMG by in vivo cleavage of the circulating anti-AChR antibodies into Fab fragments. EAMG was induced in 4-week-old female Lewis rats by i.p. injection of anti-MIR mAb35. A total of 0·75 mg of papain was given as one or three injections 3–7 h after MoAb injection. The mAb35 + papain-treated animals developed mild weakness during the first 30 h and subsequently recovered, while all animals that received only mAb35 developed severe myasthenic symptoms and died within 24–30 h. Animals treated only with papain showed no apparent side effects for up to 2 months. Serum anti-AChR levels in mAb35 + papain-treated rats decreased within a few hours, whereas in non-papain-treated rats they remained high for at least 30 h. Muscle AChR in mAb35 + papain-treated animals was partially protected from antibody-mediated degradation. These results show that treatment of rats with papain can prevent passively transferred EAMG without any apparent harm to the animals, and suggest a potential therapeutic use for proteolytic enzymes in myasthenia gravis. PMID:10792389

  8. Myasthenia gravis - resources

    MedlinePlus

    Resources - myasthenia gravis ... The following organizations provide information on myasthenia gravis : Myasthenia Gravis Foundation of America -- www.myasthenia.org National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/disorders/myasthenia_ ...

  9. Strategies for Treating Autoimmunity Novel Insights from Experimental Myasthenia Gravis

    PubMed Central

    Meriggioli, Matthew N.; Sheng, Jiarong; Li, Liangcheng; Prabhakar, Bellur S.

    2009-01-01

    Current treatments for myasthenia gravis (MG) rely upon the administration of immunosuppressive agents which result in global, nonspecific attenuation of the immune response. An alternative approach would be to attempt to design therapies that specifically dampen autoreactivity without affecting general immunity. Recently, dendritic cells (DCs) have been shown to possess potent capabilities to tolerize T cells in an antigen-specific manner. We have observed that the selective activation of particular subsets of DCs utilizing granulocyte-macrophage colony-stimulating factor (GM-CSF) had profound effects on the induction of experimental autoimmune myasthenia gravis (EAMG). Specifically, treatment with GM-CSF effectively suppressed the induction of EAMG and down-modulated anti-AChR T cell and pathogenic antibody responses. These effects were associated with the activation of tolerogenic DCs, the enhanced production of suppressive cytokines, such as IL-10, and the mobilization of.CD4+ CD2S+ and FoxP3+ regulatory T cells (Tregs). We have further shown that GM-CSF effectively ameliorates clinical disease severity in mice with active, ongoing EAMG. Based on these observations, we hypothesize that the selective activation of particular DC subsets in vivo using pharmacologic agents, like GM-CSF, can suppress ongoing anti-AChR immune responses by mobilizing antigen-specific Tregs capable of suppressing autoimmune MG. PMID:18567878

  10. Curcumin ameliorates experimental autoimmune myasthenia gravis by diverse immune cells.

    PubMed

    Wang, Shan; Li, Heng; Zhang, Min; Yue, Long-Tao; Wang, Cong-Cong; Zhang, Peng; Liu, Ying; Duan, Rui-Sheng

    2016-07-28

    Curcumin is a traditional Asian medicine with diverse immunomodulatory properties used therapeutically in the treatment of many autoimmune diseases. However, the effects of curcumin on myasthenia gravis (MG) remain undefined. Here we investigated the effects and potential mechanisms of curcumin in experimental autoimmune myasthenia gravis (EAMG). Our results demonstrated that curcumin ameliorated the clinical scores of EAMG, suppressed the expression of T cell co-stimulatory molecules (CD80 and CD86) and MHC class II, down-regulated the levels of pro-inflammatory cytokines (IL-17, IFN-γ and TNF-α) and up-regulated the levels of the anti-inflammatory cytokine IL-10, shifted the balance from Th1/Th17 toward Th2/Treg, and increased the numbers of NKR-P1(+) cells (natural killer cell receptor protein 1 positive cells, including NK and NKT cells). Moreover, the administration of curcumin promoted the differentiation of B cells into a subset of B10 cells, increased the anti-R97-166 peptide IgG1 levels and decreased the relative affinity indexes of anti-R97-116 peptide IgG. In summary, curcumin effectively ameliorate EAMG, indicating that curcumin may be a potential candidate therapeutic agent for MG. PMID:27181511

  11. Combined short-term immunotherapy for experimental autoimmune myasthenia gravis

    SciTech Connect

    Pestronk, A.; Drachman, D.B.; Teoh, R.; Adams, R.N.

    1983-08-01

    A therapeutic strategy was designed to eliminate the humoral immune response to acetylcholine receptor (AChR) in ongoing experimental autoimmune myasthenia gravis (EAMG). Rats with EAMG were treated with a protocol consisting of three components: (1) A single high dose of cyclophosphamide (200 mg/kg) was used to produce a rapid and sustained fall in the anti-AChR antibody levels by preferential destruction of antibody-producing B-lymphocytes. ''Memory'' lymphocytes were not eliminated by cyclophosphamide. (2) Irradiation (600 rads) was used to eliminate the ''memory'' cells. It eliminated the anamnestic response to a challenge with the antigen AChR. (3) Bone marrow transplantation was used to repopulate the hematopoietic system after the otherwise lethal dose of cyclophosphamide. We used bone marrow from syngeneic rats with active EAMG to simulate an autologous transplant. Rats with EAMG treated with this combined protocol showed a prompt and sustained fall in the anti-AChR antibody levels and had no anamnestic response to a challenge with AChR. Thus, an affected animal's own marrow could be stored and used later for repopulation after cyclophosphamide-irradiation treatment. This treatment eliminates the animal's ongoing immune responses and reconstitutes the immune system in its original state. The success of this approach suggests that, if their safety could be established, similar ''curative'' strategies might be developed for the treatment of patients with severe antibody-mediated autoimmune disorders, such as myasthenia gravis.

  12. Myasthenia Gravis

    MedlinePlus

    ... Funding Information Research Programs Training & Career Awards Enhancing Diversity Find People About NINDS NINDS Myasthenia Gravis Information ... News From NINDS | Find People | Training | Research | Enhancing Diversity Careers@NINDS | FOIA | Accessibility Policy | Contact Us | Privacy ...

  13. Autoimmune myasthenia gravis and dysautonomia in a dog.

    PubMed

    Gajanayake, I; Niessen, S J M; Cherubini, G B; Shelton, G D

    2008-11-01

    A two-year-old male entire border collie dog was evaluated for a short history of mixed bowel diarrhoea, coughing, vomiting and stranguria. Physical examination revealed dyspnoea with increased ventral lung sounds and a flaccidly distended bladder. Neurological examination revealed poor pupillary light reflexes, an absent gag reflex and a poor anal tone. Thoracic radiography was consistent with megaoesophagus and aspiration pneumonia. Clinicopathological testing revealed an elevated muscular nicotinic acetylcholine receptor antibody titre. The dog was euthanased because of clinical deterioration. Cerebrospinal fluid (CSF) collected immediately post-mortem revealed macrophagic pleocytosis. Post-mortem histopathological examination was consistent with dysautonomia. This is the first report of coexisting autoimmune myasthenia gravis and dysautonomia in a non-human species. The concomitant diseases may suggest a common immunopathological aetiology. PMID:18684149

  14. Vaccines against myasthenia gravis

    PubMed Central

    Berrih-Aknin, Sonia; Fuchs, Sara; Souroujon, Miriam C

    2007-01-01

    Myasthenia gravis (MG) is an autoimmune disease mediated by antibodies to nicotinic acetylcholine receptor (AChR) interfering with the neuromuscular transmission. Experimental autoimmune MG serves as an excellent animal model to study possible therapeutic modalities for MG. This review will focus on the different ways to turn off the autoimmune response to AChR, which results in suppression of myasthenia. This paper will describe the use of fragments or peptides derived from the AChR, antigen-presenting cells and anti-T cell receptor antibodies, and will discuss the underlying mechanisms of action. Finally, the authors propose new promising therapeutic prospects, including treatment based on the modulation of regulatory T cells, which have recently been found to be functionally defective in MG patients. PMID:16018742

  15. Myasthenia Gravis Foundation of America

    MedlinePlus

    ... Gravis (gMG). In the study, the primary efficacy endpoint of change from baseline in Myasthenia Gravis Activities ... significance. However, the first prospectively defined secondary efficacy endpoint of change from baseline in Quantitative Myasthenia Gravis ( ...

  16. The role of antibodies in myasthenia gravis.

    PubMed

    De Baets, M; Stassen, M H W

    2002-10-15

    Myasthenia gravis is an autoimmune disease associated with antibodies directed to the postsynaptic acetylcholine receptor. These antibodies reduce the number of receptors. Autoantibodies against AChR and other muscle antigens can be used for the diagnosis of myasthenia gravis and related disorders. The origin and the role of these antibodies in the disease are discussed. Experimental autoimmune myasthenia gravis, an experimental model closely mimicking the disease, has provided answers to many questions about the role of antibodies, complement macrophages and AChR anchor proteins. Genetically modified anti-AChR antibodies may also be used in the future to treat myasthenia. PMID:12220686

  17. ROCK inhibitor abolishes the antibody response in experimental autoimmune myasthenia gravis.

    PubMed

    Li, Heng; Zhang, Min; Wang, Cong-Cong; Li, Xiao-Li; Zhang, Peng; Yue, Long-Tao; Miao, Shuai; Dou, Ying-Chun; Li, Yan-Bin; Duan, Rui-Sheng

    2016-07-01

    The Rho/Rho kinase (ROCK) pathway serves as molecular switches in many biological processes including the immune response. ROCK inhibitors lead to amelioration of some autoimmune diseases. The present study was designed to define whether a selective ROCK inhibitor, fasudil, was effective in experimental autoimmune myasthenia gravis (EAMG) and investigate the underlying mechanisms. Here we found fasudil effectively attenuated the development of ongoing EAMG. Fasudil abolished the antibody production and function by decreasing follicular helper T cells and CD19(+) B cells, especially germinal center B cells. Moreover, fasudil reduced the expression of CD80 on lymph node mononuclear cells. These findings suggest the inhibition of ROCK might be a potential therapeutic strategy for antibody-mediated autoimmune diseases. PMID:27168379

  18. Congenital myasthenia gravis.

    PubMed

    Nizamani, Noor Bakht; Talpur, Khalid Iqbal; Memon, Mariya Nazish

    2013-07-01

    Congenital myasthenia gravis is caused by genetic mutations affecting neuromuscular transmission, characterized by muscle weakness usually starting in childhood. A two and a half years old male child presented with bilateral ptosis and hoarseness of voice. The symptoms progressed giving the clinical impression of congenital myasthenia gravis. A series of tests were done including Ice Pack Test, acetylcholine receptor antibody test, trial of steroids and finally neostigmine test which confirmed the diagnosis. This case illustrates the challenges in diagnosing congenital myasthenia gravis and highlights the potential benefits of neostigmine test in its diagnosis. PMID:23823963

  19. Silencing miR-146a influences B cells and ameliorates experimental autoimmune myasthenia gravis

    PubMed Central

    Zhang, JunMei; Jia, Ge; Liu, Qun; Hu, Jue; Yan, Mei; Yang, BaiFeng; Yang, Huan; Zhou, WenBin; Li, Jing

    2015-01-01

    MicroRNAs have been shown to be important regulators of immune homeostasis as patients with aberrant microRNA expression appeared to be more susceptible to autoimmune diseases. We recently found that miR-146a was up-regulated in activated B cells in response to rat acetylcholine receptor (AChR) α-subunit 97-116 peptide, and this up-regulation was significantly attenuated by AntagomiR-146a. Our data also demonstrated that silencing miR-146a with its inhibitor AntagomiR-146a effectively ameliorated clinical myasthenic symptoms in mice with ongoing experimental autoimmune myasthenia gravis. Furthermore, multiple defects were observed after miR-146a was knocked down in B cells, including decreased anti-R97-116 antibody production and class switching, reduced numbers of plasma cells, memory B cells and B-1 cells, and weakened activation of B cells. Previously, miR-146a has been identified as a nuclear factor-κB-dependent gene and predicted to base pair with the tumour necrosis factor receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1) genes to regulate the immune response. However, our study proved that miR-146a inhibition had no effect on the expression of TRAF6 and IRAK1 in B cells. This result suggests that the function of miR-146a in B cells does not involve these two target molecules. We conclude that silencing miR-146a exerts its therapeutic effects by influencing the B-cell functions that contribute to the autoimmune pathogenesis of myasthenia gravis. PMID:24962817

  20. Treatment for Myasthenia Gravis (MG)

    MedlinePlus

    ... are individualized There are many effective treatments for myasthenia gravis. Spontaneous improvement and even remission (although uncommon) ... Created by Kellen Interactive Web Design © copyright 2010 Myasthenia Gravis Foundation of America, Inc.

  1. Role of tolerogen conformation in induction of oral tolerance in experimental autoimmune myasthenia gravis.

    PubMed

    Im, S H; Barchan, D; Souroujon, M C; Fuchs, S

    2000-10-01

    We recently demonstrated that oral or nasal administration of recombinant fragments of the acetylcholine receptor (AChR) prevents the induction of experimental autoimmune myasthenia gravis (EAMG) and suppresses ongoing EAMG in rats. We have now studied the role of spatial conformation of these recombinant fragments in determining their tolerogenicity. Two fragments corresponding to the extracellular domain of the human AChR alpha-subunit and differing in conformation were tested: Halpha1-205 expressed with no fusion partner and Halpha1-210 fused to thioredoxin (Trx), and designated Trx-Halpha1-210. The conformational similarity of the fragments to intact AChR was assessed by their reactivity with alpha-bungarotoxin and with anti-AChR mAbs, specific for conformation-dependent epitopes. Oral administration of the more native fragment, Trx-Halpha1-210, at the acute phase of disease led to exacerbation of EAMG, accompanied by an elevation of AChR-specific humoral and cellular reactivity, increased levels of Th1-type cytokines (IL-2, IL-12), decreased levels of Th2 (IL-10)- or Th3 (TGF-beta)-type cytokines, and higher expression of costimulatory factors (CD28, CTLA4, B7-1, B7-2, CD40L, and CD40). On the other hand, oral administration of the less native fragments Halpha1-205 or denatured Trx-Halpha1-210 suppressed ongoing EAMG and led to opposite changes in the immunological parameters. It thus seems that native conformation of AChR-derived fragments renders them immunogenic and immunopathogenic and therefore not suitable for treatment of myasthenia gravis. Conformation of tolerogens should therefore be given careful attention when considering oral tolerance for treatment of autoimmune diseases. PMID:11034361

  2. IgG1 deficiency exacerbates experimental autoimmune myasthenia gravis in BALB/c mice

    PubMed Central

    Huda, Ruksana; Strait, Richard T.; Tüzün, Erdem; Finkelman, Fred D.; Christadoss, Premkumar

    2015-01-01

    Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to neuromuscular junction (NMJ) damage by anti-acetylcholine receptor (AChR) auto-antibodies and complement. In experimental autoimmune myasthenia gravis (EAMG), which is induced by immunization with Torpedo AChR in CFA, anti-AChR IgG2b and IgG1 are the predominant isotypes in the circulation. Complement activation by isotypes such as IgG2b plays a crucial role in EAMG pathogenesis; this suggested the possibility that IgG1, which does not activate complement through the classical pathway, may suppress EAMG. In this study, we show that AChR-immunized BALB/c mice genetically deficient for IgG1 produce higher levels of complement-activating isotypes of anti-AChR, especially IgG3 and IgG2a, and develop increased IgG3/IgG2a deposits at the NMJ, as compared to wild type (WT) BALB/c mice. Consistent with this, AChR-immunized IgG1−/− BALB/c mice lose muscle strength and muscle AChR to a greater extent than AChR-immunized WT mice. These observations demonstrate that IgG1 deficiency leads to increased severity of EAMG associated with an increase in complement activating IgG isotypes. Further studies are needed to dissect the specific role or mechanism of IgG1 in limiting EAMG and that of EAMG exacerbating role of complement activating IgG3 and IgG2a in IgG1 deficiency. PMID:25867470

  3. Recombinant IgG2a Fc (M0451) Multimers Effectively Suppress Experimental Autoimmune Myasthenia Gravis

    PubMed Central

    Thiruppathi, Muthusamy; Sheng, Jian Rong; Li, Liangcheng; Prabhakar, Bellur S.; Meriggioli, Matthew N.

    2014-01-01

    Myasthenia gravis (MG) is an autoimmune disorder caused by target-specific pathogenic antibodies directed toward postsynaptic neuromuscular junction (NMJ) proteins, most commonly the skeletal muscle nicotinic acetylcholine receptor (AChR). In MG, high-affinity anti-AChR Abs binding to the NMJ lead to loss of functional AChRs, culminating in neuromuscular transmission failure and myasthenic symptoms. Intravenous immune globulin (IVIg) has broad therapeutic application in the treatment of a range of autoimmune diseases, including MG, although its mechanism of action is not clear. Recently, the anti-inflammatory and anti-autoimmune activities of IVIg have been attributed to the IgG Fc domains. Soluble immune aggregates bearing intact Fc fragments have been shown to be effective treatment for a number of autoimmune disorders in mice, and fully recombinant multimeric Fc molecules have been shown to be effective in treating collagen-induced arthritis, murine immune thrombocytopenic purpura, and experimental inflammatory neuritis. In this study, a murine model of MG (EAMG) was used to study the effectiveness of this novel recombinant polyvalent IgG2a Fc (M045) in treating established myasthenia, with a direct comparison to treatment with IVIg. M045 treatment had profound effects on the clinical course of EAMG, accompanied by down-modulation of pathogenic antibody responses. These effects were associated with reduced B cell activation and T cell proliferative responses to AChR, an expansion in the population of FoxP3+ regulatory T cells, and enhanced production of suppressive cytokines, such as IL-10. Treatment was at least as effective as IVIg in suppressing EAMG, even at doses 25–30 fold lower. Multimeric Fc molecules offer the advantages of being recombinant, homogenous, available in unlimited quantity, free of risk from infection and effective at significantly reduced protein loads, and may represent a viable therapeutic alternative to polyclonal IVIg. PMID:24388113

  4. Suppression of experimental autoimmune myasthenia gravis by autologous T regulatory cells.

    PubMed

    Aricha, Revital; Reuveni, Debby; Fuchs, Sara; Souroujon, Miriam C

    2016-02-01

    Adoptive transfer of regulatory T (Treg) cells have been employed effectively for suppression of several animal models for autoimmune diseases. In order to employ Treg cell therapy in patients, it is necessary to generate Treg cells from the patient's own cells (autologous) that would be able to suppress effectively the disease in vivo, upon their reintroduction to the patient. Towards this objective, we report in the present study on a protocol for a successful immune-regulation of experimental autoimmune myasthenia gravis (EAMG) by ex vivo--generated autologous Treg cells. For this protocol bone marrow (BM) cells, are first cultured in the presence of GM-CSF, giving rise to a population of CD11c(+)MHCII(+)CD45RA(+)CD8(-) DCs (BMDCs). Splenic CD4(+) T cells are then co-cultured with the differentiated BM cells and expand to 90% of Foxp3(+) Treg cells. In vitro assay exhibits a similar dose dependent manner in the suppression of T effector cells proliferation between Treg cells obtained from either healthy or sick donors. In addition, both Treg cells inhibit similarly the secretion of IFN-γ from activated splenocytes. Administration of 1 × 10(6) ex-vivo generated Treg cells, I.V, to EAMG rats, modulates the disease following a single treatment, given 3 days or 3 weeks after disease induction. Similar disease inhibition was achieved when CD4 cells were taken from either healthy or sick donors. The disease suppression was accompanied by reduced levels of total AChR specific antibodies in the serum. Moreover, due to the polyclonality of the described Treg cell, we have examined whether this treatment approach could be also employed for the treatment of other autoimmune diseases involving Treg cells. Indeed, we demonstrated that the ex-vivo generated autologous Treg cells suppress Adjuvant Arthritis (AA) in rats. This study opens the way for the application of induced autologous Treg cell therapy for myasthenia gravis, as well as for other human autoimmune diseases

  5. Overview of myasthenia gravis.

    PubMed

    Arora, Yeeshu; Li, Yuebing

    2013-01-01

    Myasthenia gravis is an antibody-mediated disorder of neuromuscular transmission that is characterized by weakness and fatigue of voluntary muscles. Weakness may be ocular, bulbar, or generalized. Diagnostic evaluation of patients consists of bedside assessment, antibody testing, and electrophysiologic studies. Various therapeutic options are available, which consist of anticholinesterase inhibitors for symptomatic management, immunosuppressive agents as maintenance therapy, and thymectomy. Plasmapheresis and intravenous immunoglobulin are used in patients in crisis or those with rapidly worsening or refractory symptoms. In our article, we elaborate on key aspects of the epidemiology, pathogenesis, diagnostic evaluation, and therapeutic options for patients with myasthenia gravis. PMID:24145588

  6. Assays for myasthenia gravis

    SciTech Connect

    Lindstrom, J.M.

    1988-12-06

    This patent describes an improvement in a process for diagnosing myasthenia gravis. The process comprises the steps of preparing a complex of acetycholine receptor protein, toxin and a radioactive isotope, incubating the complex with a serum sample from a patient so as to join antibodies engendered in connection with myasthenia gravis to the complex, precipitating the complex joined with antibody with anti-immunoglobulin and measuring radioactivity, from the radioactive isotope, of the precipitated complex. The improvement is that the acetylcholine receptor protein is derived from cells of the TE671 Line.

  7. [Umbilical cord mesenchymal stem cell transplantation for treatment of experimental autoimmune myasthenia gravis in rats].

    PubMed

    Yu, Jing-Xia; Chen, Fang; Sun, Jun; Wang, Ji-Ming; Zhao, Qin-Jun; Ren, Xin-Jun; Ma, Feng-Xia; Yang, Shao-Guang; Han, Zhi-Bo; Han, Zhong-Chao

    2011-06-01

    Umbilical cord mesenchymal stem cell (UCMSC) transplantation has been widely used in the treatment of a variety of diseases due to their advantages such as abundant resources, low immunogenicity and large ex vivo expansion capacity. This study was aimed to investigate the effects of UCMSC on experimental autoimmune myasthenia gravis (EAMG) rats. The distribution of human-derived cells was observed by immunofluorescence method, the effect of MSC on B-cell in situ-secreted antibodies was assayed by ELISPOT, the secreted IFN-γ level was detected by using Transwell test. The results showed that UCMSC were able to migrate to inflammation region and lymph nudes, moreover human-derived cells could be detected in medulla zone of lymph nudes. In vitro in situ detection of AchR specific antibody secretion revealed that the full contact of MSC with lymphnode-derived lymphocytes could effectively inhibit production of AchR antibody. Transwell test indicated that the direct contact of UCMSC with CD4 T cells could effectively decrease production of IFN-γ, which modulated the unbalance between Th1/Th2 to a certain extent. It is concluded that UCMSC can regulate the immune system by direct cell-cell contact or/and release of cytokines, which bring a new insight into knowledge about MSC-based therapy for EAMG. PMID:21729563

  8. Coexistent autoimmune autonomic ganglionopathy and myasthenia gravis associated with non-small-cell lung cancer.

    PubMed

    Peltier, Amanda C; Black, Bonnie K; Raj, Satish R; Donofrio, Peter; Robertson, David; Biaggioni, Italo

    2010-03-01

    We report the case of a 55-year-old man with non-small-cell lung cancer who underwent radiation, chemotherapy with carbotaxol and paclitaxel, and left upper lobe removal 2 years prior to evaluation. He was referred for disabling orthostatic hypotension (113/69 mm Hg supine and 66/47 mm Hg standing after 10 minutes) without a compensatory heart rate increase (57 to 59 beats per minute), fatigue, and constipation with episodes of ileus. Clinical examination showed mild ptosis bilaterally, fatiguable neck flexor weakness, and hip flexor weakness. Blood pressure response to Valsalva maneuver was abnormal with an absence of phase 4 overshoot and a Valsalva heart rate ratio of 1.04. Plasma norepinephrine level was low (79 pg/ml supine, 330 pg/ml standing). Single-fiber electromyography of the right extensor digitorum communis revealed normal mean consecutive difference (jitter) but several pairs exceeded a jitter of 100 mus. Antibodies against muscle acetylcholine receptor [(AChR) 0.66 nmol/L, normal <0.02 nmol/L] and ganglionic AChR (0.34 nmol/L, normal <0.02 nmol/L) were present. Treatment with plasma exchange normalized responses to standing posture (105/68 supine to 118/82 mm Hg standing, 66 to 79 beats per minute), to Valsalva (normal blood pressure overshoot, hazard ratio 1.47), norepinephrine (194 pg/ml supine, 763 pg/ml standing), and jitter measurements. We conclude that autoimmune autonomic ganglionopathy and myasthenia gravis can coexist and suggest that the latter should be excluded in patients with autoimmune autonomic ganglionopathy who complain of fatigue that shows improvement with non-supine rest. PMID:19882640

  9. Suppression of experimental myasthenia gravis, a B cell-mediated autoimmune disease, by blockade of IL-18.

    PubMed

    Im, S H; Barchan, D; Maiti, P K; Raveh, L; Souroujon, M C; Fuchs, S

    2001-10-01

    Interleukin-18 (IL-18) is a pleiotropic proinflammatory cytokine that plays an important role in interferon gamma (IFN-gamma) production and IL-12-driven Th1 phenotype polarization. Increased expression of IL-18 has been observed in several autoimmune diseases. In this study we have analyzed the role of IL-18 in an antibody-mediated autoimmune disease and elucidated the mechanisms involved in disease suppression mediated by blockade of IL-18, using experimental autoimmune myasthenia gravis (EAMG) as a model. EAMG is a T cell-regulated, antibody-mediated autoimmune disease in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. Th1- and Th2-type responses are both implicated in EAMG development. We show that treatment by anti-IL-18 during ongoing EAMG suppresses disease progression. The protective effect can be adoptively transferred to naive recipients and is mediated by increased levels of the immunosuppressive Th3-type cytokine TGF-beta and decreased AChR-specific Th1-type cellular responses. Suppression of EAMG is accompanied by down-regulation of the costimulatory factor CD40L and up-regulation of CTLA-4, a key negative immunomodulator. Our results suggest that IL-18 blockade may potentially be applied for immunointervention in myasthenia gravis. PMID:11641240

  10. Thymus irradiation for myasthenia gravis

    SciTech Connect

    Currier, R.D.; Routh, A.; Hickman, B.T.; Douglas, M.A.

    1983-01-01

    Twenty-eight patients with progressive myasthenia gravis without thymoma received treatment of 3000 rads (30 Gy) to the anterior mediastinum, and a followup was conducted for five to 18 years. Twenty-four patients had generalized myasthenia, and four had ocular myasthenia gravis. Twenty patients with generalized myasthenia survived the several month post-treatment period and improved, but four died during that period. The improvement lasted a median of 1.5 years, and older patients had longer remissions than younger patients. The four patients who had ocular myasthenia did not change after treatment. Mediastinal irradiation produces a temporary remission in generalized myasthenia.

  11. Thymomatous myasthenia gravis.

    PubMed

    Pandit, L; Rao, S N

    1995-08-01

    Ten cases of thymoma associated myasthenia were seen in the last 7 years. They constitute 17.2% of all cases of Myasthenia gravis seen during the same period. Five of these patients presented in the third decade, all of them presenting with acute generalised Myasthenia (Osserman stage-III). Two patients presented with tumour related symptoms of chest pain, cough and dyspnea both of them having large, invasive and partially resectable tumours. Five patients underwent complete thymectomy and 3 patients underwent partial resection of tumour. Two patients underwent radiotherapy subsequently. Histologically, mixed lymphoepithelial tumours were common (70%). Tumour recurrence was seen in one patient. Two patients died, one in the post operative period. The surviving 8 patients followed up over 1-8 years remained in partial remission, on maintenance dose of steroids. The special problems related to thymomatous MG and practical approach to management are highlighted. PMID:8772974

  12. Prevention of passively transferred experimental autoimmune myasthenia gravis by a phage library-derived cyclic peptide

    PubMed Central

    Venkatesh, Natarajan; Im, Sin-Heyog; Balass, Moshe; Fuchs, Sara; Katchalski-Katzir, Ephraim

    2000-01-01

    Many pathogenic antibodies in myasthenia gravis (MG) and its animal model, experimental autoimmune MG (EAMG), are directed against the main immunogenic region (MIR) of the acetylcholine receptor (AcChoR). These antibodies are highly conformation dependent; hence, linear peptides derived from native receptor sequences are poor candidates for their immunoneutralization. We employed a phage-epitope library to identify peptide-mimotopes capable of preventing the pathogenicity of the anti-MIR mAb 198. We identified a 15-mer peptide (PMTLPENYFSERPYH) that binds specifically to mAb 198 and inhibits its binding to AcChoR. A 10-fold increase in the affinity of this peptide was achieved by incorporating flanking amino acid residues from the coat protein as present in the original phage library. This extended peptide (AEPMTLPENYFSERPYHPPPP) was constrained by the addition of cysteine residues on both ends of the peptide, thus generating a cyclic peptide that inhibited the binding of mAb 198 to AcChoR with a potency that is three orders of magnitude higher when compared with the parent library peptide. This cyclic peptide inhibited the in vitro binding of mAb 198 to AcChoR and prevented the antigenic modulation of AcChoR caused by mAb 198 in human muscle cell cultures. The cyclic peptide also reacted with several other anti-MIR mAbs and the sera of EAMG rats. In addition, this peptide blocked the ability of mAb 198 to passively transfer EAMG in rats. Further derivatization of the cyclic peptide may aid in the design of suitable synthetic mimotopes for modulation of MG. PMID:10639153

  13. "Warming yang and invigorating qi" acupuncture alters acetylcholine receptor expression in the neuromuscular junction of rats with experimental autoimmune myasthenia gravis.

    PubMed

    Huang, Hai-Peng; Pan, Hong; Wang, Hong-Feng

    2016-03-01

    Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction. "Warming yang and invigorating qi" acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis. However, few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction. Here, we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following "warming yang and invigorating qi" acupuncture therapy. Needles were inserted at acupressure points Shousanli (LI10), Zusanli (ST36), Pishu (BL20), and Shenshu (BL23) once daily for 7 consecutive days. The treatment was repeated after 1 day of rest. We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment. This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide. These findings suggest that "warming yang and invigorating qi" acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis. PMID:27127487

  14. “Warming yang and invigorating qi” acupuncture alters acetylcholine receptor expression in the neuromuscular junction of rats with experimental autoimmune myasthenia gravis

    PubMed Central

    Huang, Hai-peng; Pan, Hong; Wang, Hong-feng

    2016-01-01

    Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction. “Warming yang and invigorating qi” acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis. However, few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction. Here, we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following “warming yang and invigorating qi” acupuncture therapy. Needles were inserted at acupressure points Shousanli (LI10), Zusanli (ST36), Pishu (BL20), and Shenshu (BL23) once daily for 7 consecutive days. The treatment was repeated after 1 day of rest. We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment. This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide. These findings suggest that “warming yang and invigorating qi” acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis. PMID:27127487

  15. Myasthenia Gravis: Medical Aspects

    PubMed Central

    Zeldowicz, Ludmila R.; Buckler, William St. John

    1965-01-01

    The diagnosis of myasthenia gravis is often difficult and calls for a broader use of pharmacological and electrodiagnostic tests. The decamethonium-edrophonium test, which has proved superior to other procedures for this purpose, is based on neurophysiological principles and depicts the behaviour of the neuromuscular junction. A state of resistance to depolarizing agents in the limited form of myasthenia and a state of a non-depolarizing (competitive) block in advanced cases has been shown. This test has demonstrated that the neuromuscular defect exists throughout the skeletal musculature, including muscles clinically unaffected. It produced no false-positive results either in normal or neurasthenic persons or in patients with neurological diseases with myasthenic symptoms. In a patient with botulism and in a patient with ocular palsies from brain-stem encephalitis the edrophonium test gave a false-positive result, while the decamethonium-edrophonium test was negative. Diagnosis, treatment and management of myasthenic emergencies are described. PMID:14323662

  16. Muscle autoantibodies in myasthenia gravis: beyond diagnosis?

    PubMed Central

    Meriggioli, Matthew N; Sanders, Donald B

    2012-01-01

    Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. A number of molecules, including ion channels and other proteins at the neuromuscular junction, may be targeted by autoantibodies leading to abnormal neuromuscular transmission. In approximately 85% of patients, autoantibodies, directed against the postsynaptic nicotinic acetylcholine receptor can be detected in the serum and confirm the diagnosis, but in general, do not precisely predict the degree of weakness or response to therapy. Antibodies to the muscle-specific tyrosine kinase are detected in approximately 50% of generalized myasthenia gravis patients who are seronegative for anti-acetylcholine receptor antibodies, and levels of anti-muscle-specific tyrosine kinase antibodies do appear to correlate with disease severity and treatment response. Antibodies to other muscle antigens may be found in the subsets of myasthenia gravis patients, potentially providing clinically useful diagnostic information, but their utility as relevant biomarkers (measures of disease state or response to treatment) is currently unclear. PMID:22882218

  17. Evidence of enhanced recombinant interleukin-2 sensitivity in thymic lymphocytes from patients with myasthenia gravis: possible role in autoimmune pathogenesis.

    PubMed

    Cohen-Kaminsky, S; Levasseur, P; Binet, J P; Berrih-Aknin, S

    1989-09-01

    We evaluated the activation state of thymic lymphocytes in patients with myasthenia gravis (MG) by cytofluorographic analysis of CD25 expression and by testing their sensitivity to recombinant interleukin-2 (rIL-2) in the absence of any known previous stimulation. We detected no phenotypic signs of activation in fresh MG thymic lymphocyte suspensions, while functional signs of activation were reflected in a significantly higher sensitivity to rIL-2 in MG patients than in controls. The responses to rIL-2 were time- and dose-dependent, were inhibited by a blocking anti-IL-2 receptor antibody, and were associated with an increase in CD25+ T cells in both patients and controls. The T cells with functional signs of previous activation may represent autoreactive cells involved in the autoimmune process and confirm thymus gland hyperactivity in MG. These cells could result from primary autosensitization against the thymic acetylcholine receptor (AChR)-like molecule or from altered migration of peripheral activated cells into an abnormal thymic environment. Our results also provide a clue for understanding the effect of thymectomy in myasthenia gravis. PMID:2808688

  18. MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK.

    PubMed

    Küçükerden, Melike; Huda, Ruksana; Tüzün, Erdem; Yılmaz, Abdullah; Skriapa, Lamprini; Trakas, Nikos; Strait, Richard T; Finkelman, Fred D; Kabadayı, Sevil; Zisimopoulou, Paraskevi; Tzartos, Socrates; Christadoss, Premkumar

    2016-06-15

    Sera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1+, IgG2+ and IgG3+ peripheral blood B cells in MuSK-immunized wild-type (WT) mice. Moreover, MuSK-immunized IgG1 knockout (KO) and WT mice showed similar EAMG severity, serum MuSK-Ab levels, muscle acetylcholine receptor concentrations, neuromuscular junction immunoglobulin and complement deposit ratios. IgG1 and IgG3 were the predominant anti-MuSK isotypes in WT and IgG1 KO mice, respectively. These observations demonstrate that non-IgG1 isotypes can mediate MuSK-EAMG pathogenesis. PMID:27235354

  19. Modulation of the anti-acetylcholine receptor response and experimental autoimmune myasthenia gravis by recombinant fragments of the acetylcholine receptor.

    PubMed

    Barchan, D; Asher, O; Tzartos, S J; Fuchs, S; Souroujon, M C

    1998-02-01

    Myasthenia gravis (MG) is a neuromuscular disorder of man caused by a humoral response to the acetylcholine receptor (AChR). Most of the antibodies in MG and in experimental autoimmune myasthenia gravis (EAMG) are directed to the extracellular portion of the AChR alpha subunit, and within it, primarily to the main immunogenic region (MIR). We have cloned and expressed recombinant fragments, corresponding to the entire extracellular domain of the AChR alpha subunit (H alpha1-210), and to portions of it that encompass either the MIR (H alpha1-121) or the ligand binding site of AChR (H alpha122-210), and studied their ability to interfere with the immunopathological anti-AChR response in vitro and in vivo. All fragments were expressed as fusion proteins with glutathione S-transferase. Fragments H alpha1-121 and H alpha1-210 protected AChR in TE671 cells against accelerated degradation induced by the anti-MIR monoclonal antibody (mAb)198 in a dose-dependent manner. Moreover, these fragments had a similar effect on the antigenic modulation of AChR by other anti-MIR mAb and by polyclonal rat anti-AChR antibodies. Fragments H alpha1-121 and H alpha1-210 were also able to modulate in vivo muscle AChR loss and development of clinical symptoms of EAMG, passively transferred to rats by mAb 198. Fragment H alpha122-210 did not have such a protective activity. Our results suggest that the appropriate recombinant fragments of the human AChR may be employed in the future for antigen-specific therapy of myasthenia. PMID:9521072

  20. Lymphocyte function in myasthenia gravis.

    PubMed Central

    Kawanami, S; Kanaide, A; Itoyama, Y; Kuroiwa, Y

    1979-01-01

    Mitogen-induced blastoid transformation of peripheral blood lymphocytes from patients with myasthenia gravis was studied using a microplate culture technique and evaluated with 3H-thymidine incorporation. It was found that both phytohaemagglutinin and pokeweed mitogen responses decreased significantly in patients with myasthenia gravis. In myasthenic crisis, indices of stimulation by phytohaemagglutination became very low. The autologous plasma neither inhibited nor facilitated mitogenic responses of lymphocytes. The decreased mitogen responsiveness of lymphocytes suggests that part of the T lymphocyte function is subnormal in myasthenia. PMID:490180

  1. CD1dhiCD5+ B cells Expanded by GM-CSF in Vivo Suppress Experimental Autoimmune Myasthenia Gravis

    PubMed Central

    Sheng, Jian Rong; Quan, Songhua; Soliven, Betty

    2014-01-01

    IL-10-competent subset within CD1dhiCD5+ B cells, also known as B10 cells, has been shown to regulate autoimmune diseases. Whether B10 cells can prevent or suppress the development of experimental autoimmune myasthenia gravis (EAMG) has not been studied. In this study, we investigated whether low dose granulocyte macrophage-colony stimulating factor (GM-CSF), which suppresses EAMG, can expand B10 cells in vivo, and whether adoptive transfer of CD1dhiCD5+ B cells would prevent or suppress EAMG. We found that treatment of EAMG mice with low-dose GM-CSF increased the proportion of CD1dhiCD5+ B cells and B10 cells. In vitro co-culture studies revealed that CD1dhiCD5+ B cells altered T cell cytokine profile but did not directly inhibit T cell proliferation. On the other hand, CD1dhiCD5+ B cells inhibited B cell proliferation and its autoantibody production in an IL-10-dependent manner. Adoptive transfer of CD1dhiCD5+ B cells to mice could prevent disease as well as suppress EAMG after disease onset. This was associated with downregulation of mature dendritic cell markers and expansion of regulatory T cells resulting in the suppression of acetylcholine receptor (AChR)-specific T cell and B cell responses. Thus, our data have provided significant insights into the mechanisms underlying the tolerogenic effects of B10 cells in EAMG. These observations suggest that in vivo or in vitro expansion of CD1dhiCD5+ B cells or B10 cells may represent an effective strategy in the treatment of human myasthenia gravis. PMID:25135828

  2. Mouse models of myasthenia gravis.

    PubMed

    Ban, Joanne; Phillips, William D

    2015-01-01

    Myasthenia gravis is a muscle weakness disease characterized by autoantibodies that target components of the neuromuscular junction, impairing synaptic transmission. The most common form of myasthenia gravis involves antibodies that bind the nicotinic acetylcholine receptors in the postsynaptic membrane. Many of the remaining cases are due to antibodies against muscle specific tyrosine kinase (MuSK). Recently, autoantibodies against LRP4 (another component of the MuSK signaling complex in the postsynaptic membrane) were identified as the likely cause of myasthenia gravis in some patients. Fatiguing weakness is the common symptom in all forms of myasthenia gravis, but muscles of the body are differentially affected, for reasons that are not fully understood. Much of what we have learnt about the immunological and neurobiological aspects of the pathogenesis derives from mouse models. The most widely used mouse models involve either passive transfer of autoantibodies, or active immunization of the mouse with acetylcholine receptors or MuSK protein. These models can provide a robust replication of many of the features of the human disease. Depending upon the protocol, acute fatiguing weakness develops 2 - 14 days after the start of autoantibody injections (passive transfer) or might require repeated immunizations over several weeks (active models). Here we review mouse models of myasthenia gravis, including what they have contributed to current understanding of the pathogenic mechanisms and their current application to the testing of therapeutics. PMID:25777761

  3. Juvenile myasthenia gravis: a paediatric perspective.

    PubMed

    Finnis, Maria F; Jayawant, Sandeep

    2011-01-01

    Myasthenia gravis (MG) is an autoimmune disease in which antibodies are directed against the postsynaptic membrane of the neuromuscular junction, resulting in muscle weakness and fatigability. Juvenile myasthenia gravis (JMG) is a rare condition of childhood and has many clinical features that are distinct from adult MG. Prepubertal children in particular have a higher prevalence of isolated ocular symptoms, lower frequency of acetylcholine receptor antibodies, and a higher probability of achieving remission. Diagnosis in young children can be complicated by the need to differentiate from congenital myasthenic syndromes, which do not have an autoimmune basis. Treatment commonly includes anticholinesterases, corticosteroids with or without steroid-sparing agents, and newer immune modulating agents. Plasma exchange and intravenous immunoglobulin (IVIG) are effective in preparation for surgery and in treatment of myasthenic crisis. Thymectomy increases remission rates. Diagnosis and management of children with JMG should take account of their developmental needs, natural history of the condition, and side-effect profiles of treatment options. PMID:22110902

  4. [Myasthenia gravis and myasthenic syndromes].

    PubMed

    Marouf, W; Sieb, J P

    2009-08-01

    Neuromuscular transmission is compromised in a variety of disorders due to immunological, toxic or congenital mechanisms. Myasthenia gravis (MG) is the most frequent among these disorders. In about 15% of cases, MG is associated with a second autoimmune disorder mainly seen in rheumatologists. Some of the drugs used in rheumatology can exacerbate MG or even trigger immunologically the occurrence of MG. In most MG patients, antibodies to the acetylcholine receptor (AChR) are present, but around 10% have AChR antibodies that are only identified by novel methods, and up to 5% have muscle-specific kinase antibodies which define a different subgroup of myasthenia. Among those MG patients with anti-AChR antibodies, a number of clinical subtypes can be identified including early-onset MG (onset

  5. [Myasthenia gravis - optimal treatment and accurate diagnosis].

    PubMed

    Gilhus, Nils Erik; Kerty, Emilia; Løseth, Sissel; Mygland, Åse; Tallaksen, Chantal

    2016-07-01

    Around 700 people in Norway have myasthenia gravis, an autoimmune disease that affects neuromuscular transmission and results in fluctuating weakness in some muscles as its sole symptom. The diagnosis is based on typical symptoms and findings, detection of antibodies and neurophysiological examination. Symptomatic treatment with acetylcholinesterase inhibitors is generally effective, but most patients also require immunosuppressive drug treatment. Antigen-specific therapy is being tested in experimental disease models. PMID:27381787

  6. [Autoantibodies in myasthenia gravis].

    PubMed

    Motomura, Masakatsu; Narita Masuda, Tomoko

    2013-04-01

    Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission mediated by pathogenic autoantibodies (Abs). Generally, patients with MG are divided into 3 groups: (1) nicotinic acetylcholine receptor antibody-positive MG (AChR-MG: 80%), (2) muscle-specific receptor tyrosine kinase antibody-positive MG (MuSK-MG: 5-10%), which are AChR-associated transmembrane post-synaptic proteins involved in AChR aggregation, and (3) double-seronegative MG. In 2011, autoantibodies against low-density lipoprotein receptor-related protein 4 (Lrp4) were identified in Japanese MG patients, and thereafter, have been reported in Germany and USA. We developed a simple technique termed Gaussia luciferase immunoprecipitation (GLIP) for detecting the antibodies to Lrp4. Our results showed that 9 generalized MG patients out of 300 without AChR Ab were positive for Lrp4 antibodies. These antibodies inhibit the binding of Lrp4 to its ligand and predominantly belong to the IgG1 subclass. In other studies, Lrp4 Ab-positive sera inhibited agrin-induced aggregation of AChRs in cultured myotubes, suggesting a pathogenic role in the dysfunction of the neuromuscular endplate. Further understanding of the structure and function of neuromuscular junction (NMJ) through newly discovered autoantibodies may provide specific clinical information and treatment for MG. PMID:23568991

  7. Treatment of myasthenia gravis: current practice and future directions.

    PubMed

    Ciafaloni, Emma; Sanders, Donald B

    2002-09-01

    Myasthenia gravis is the best understood of the autoimmune diseases and a number of treatments are currently used to produce clinical improvement. However, due to the scarcity of evidence-based and comparative data, there is still no consensus on many therapeutic issues. Even a widely accepted treatment like thymectomy has never been proven effective by a well-designed trial. These are just some of the unanswered questions: What is the best treatment algorithm and safest long-term management of myasthenia gravis? What patients are likely to benefit from thymectomy? How long should myasthenia gravis patients be treated? Is it possible to discontinue immunotherapy once remission has been achieved? What are the risks associated with long-term immunosuppression? In this article, we review current therapeutic strategies and these unresolved questions about myasthenia gravis treatment. PMID:19810991

  8. Myasthenia gravis: an update for the clinician.

    PubMed

    Sieb, J P

    2014-03-01

    This paper provides a thorough overview of the current advances in diagnosis and therapy of myasthenia gravis (MG). Nowadays the term 'myasthenia gravis' includes heterogeneous autoimmune diseases, with a postsynaptic defect of neuromuscular transmission as the common feature. Myasthenia gravis should be classified according to the antibody specificity [acetylcholine, muscle-specific receptor tyrosine kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), seronegative], thymus histology (thymitis, thymoma, atrophy), age at onset (in children; aged less than or more than 50 years) and type of course (ocular or generalized). With optimal treatment, the prognosis is good in terms of daily functions, quality of life and survival. Symptomatic treatment with acetylcholine esterase inhibition is usually combined with immunosuppression. Azathioprine still remains the first choice for long-term immunosuppressive therapy. Alternative immunosuppressive options to azathioprine include cyclosporin, cyclophosphamide, methotrexate, mycophenolate mofetil and tacrolimus. Rituximab is a promising new drug for severe generalized MG. Emerging therapy options include belimumab, eculizumab and the granulocyte- macrophage colony-stimulating factor. One pilot study on etanercept has given disappointing results. For decades, thymectomy has been performed in younger adults to improve non-paraneoplastic MG. However, controlled prospective studies on the suspected benefit of this surgical procedure are still lacking. In acute exacerbations, including myasthenic crisis, intravenous immunoglobulin, plasmapheresis and immunoadsorption are similarly effective. PMID:24117026

  9. Clinical electrophysiology in myasthenia gravis.

    PubMed Central

    Stalberg, E

    1980-01-01

    Effective diagnostic methods are of great importance in order to recognise myasthenic patients among those with muscle fatigability. Intracellular recordings are useful for research work within the field and for detailed description of the motor end-plate's physiology in the individual case. The method is not used for the routine diagnosis of myasthenia gravis. The decrement of the electrical muscle response with nerve stimulation is the most commonly used method. The diagnostic yield is higher in proximal muscles, in warmed muscles, after exercise, and after ischaemia. A significant number of patients may be undiagnosed with this technique. The mechanical response with nerve stimulation shows the same type of decrement but also an abnormal response to long stimulation. The diagnostic value of this is under dispute. Single fibre ENG needs more patient cooperation than do these tests. The diagnostic yield is significantly higher. Some patients considered to have myasthenia gravis do not show any abnormalities with this technique, particularly those with the pure ocular form. Conventional EMG is not useful for the diagnosis of myasthenia, but may be indicated in these patients when concurrent nerve or muscle disease is in question. Tests for eye movement fatique have not proved useful. Stapedius reflex fatigability is demonstrated in about the same proportion of patients as have positive SFEMG findings. The technique is not uncomfortable for the patient and requires minimal cooperation. The general usefulness must be assessed by further routine use. Even with the advent of immunological tests, neurophysiological investigations are indispensable in helping establish the diagnosis of myasthenia gravis. Discrepancies between the results comparing electrophysiological and immunological tests may indicate that myasthenia gravis is a heterogenous entity within which subgroups may be identified. PMID:6249895

  10. Ocular myasthenia gravis: A review

    PubMed Central

    Nair, Akshay Gopinathan; Patil-Chhablani, Preeti; Venkatramani, Devendra V; Gandhi, Rashmin Anilkumar

    2014-01-01

    Myasthenia gravis (MG) is a disease that affects the neuro-muscular junction resulting in classical symptoms of variable muscle weakness and fatigability. It is called the great masquerader owing to its varied clinical presentations. Very often, a patient of MG may present to the ophthalmologist given that a large proportion of patients with systemic myasthenia have ocular involvement either at presentation or during the later course of the disease. The treatment of ocular MG involves both the neurologist and ophthalmologist. Thus, the aim of this review was to highlight the current diagnosis, investigations, and treatment of ocular MG. PMID:25449931

  11. Pemphigus foliaceus exacerbated by radiation, in association with myasthenia gravis.

    PubMed

    Liebman, Tracey N; Lieberman, Miriam R; Burris, Katy

    2016-01-01

    Pemphigus foliaceus (PF) is a sporadic autoimmune blistering disease of unknown etiology. The production of immunoglobulin G4 antibodies against desmoglein-1 is responsible for the clinical manifestation of PF. We present a case of a woman with a recent diagnosis of myasthenia gravis (MG), who was also recently treated with radiation therapy for breast cancer. The clinical exam, supported by biopsy and direct immunofluorescence, were consistent with PF. We present this case to increase the awareness of the potential exacerbation or induction of PF with radiation, and of the association of PF and myasthenia gravis. Only five prior cases of radiation-exacerbated or radiation-induced PF have been reported in the literature to date. Furthermore, the co-existence of the autoimmune entities of myasthenia gravis and PF has been reported in the literature in only 9 cases and was also noted in this patient. PMID:27136623

  12. Seronegative Maternal Ocular Myasthenia Gravis and Delayed Transient Neonatal Myasthenia Gravis

    PubMed Central

    Townsel, Courtney; Keller, Rebecca; Johnson, Kendall; Hussain, Naveed; Campbell, Winston A.

    2016-01-01

    Background Myasthenia gravis (MG) is an autoimmune disorder with fluctuating muscle weakness, divided into generalized and localized (ocular) forms. Maternal antibodies to acetylcholine receptors cross the placenta and may cause transient neonatal myasthenia gravis (TNMG). We present a case of seronegative maternal ocular MG and delayed TNMG. Case A 29-year-old G3P1011 underwent cesarean birth of a male infant who developed oxygen desaturation requiring supplemental oxygen on day of life (DOL) 3. Based on the clinical course and after exclusion of other diagnoses, the infant was diagnosed with TNMG. Infant's condition improved spontaneously and he was weaned off supplemental oxygen and discharged home on DOL 12. Conclusion Infants born to mothers with seronegative localized (ocular) MG are also susceptible to TNMG which may be late in onset. PMID:26989568

  13. The CD45 77C/G allele is not associated with myasthenia gravis - a reassessment of the potential role of CD45 in autoimmunity

    PubMed Central

    2010-01-01

    Background The G allele of the CD45 77C/G SNP (rs17612648), which has previously been suggested to be associated with autoimmune disorders, was genotyped in 446 Swedish myasthenia gravis (MG) patients and 2303 matched controls. Results There was no association between the polymorphism and patient group as a whole (p = 0.199), nor with clinical subgroups. Our results add to a growing number of studies unable to find association between the 77C/G polymorphism and autoimmune disorders. One control sample, from an adult blood donor, was homozygous for the G allele, yet negative for a panel of auto-antibodies, representing the first homozygous individual studied in this respect. Conclusions The 77C/G mutation does not predispose to MG, and its role in autoimmunity may have to be re-evaluated. PMID:21067564

  14. Myasthenia Gravis Medication Information Card (Drugs to be Avoided or Used with Caution in Myasthenia Gravis)

    MedlinePlus

    ... possibility whenever a new medication is prescribed. For questions regarding medications, contact ... “Medications and Myasthenia Gravis (A Reference for Health Care Professionals.” www.myasthenia. ...

  15. Profound Olfactory Dysfunction in Myasthenia Gravis

    PubMed Central

    Leon-Sarmiento, Fidias E.; Bayona, Edgardo A.; Bayona-Prieto, Jaime; Osman, Allen; Doty, Richard L.

    2012-01-01

    In this study we demonstrate that myasthenia gravis, an autoimmune disease strongly identified with deficient acetylcholine receptor transmission at the post-synaptic neuromuscular junction, is accompanied by a profound loss of olfactory function. Twenty-seven MG patients, 27 matched healthy controls, and 11 patients with polymiositis, a disease with peripheral neuromuscular symptoms analogous to myasthenia gravis with no known central nervous system involvement, were tested. All were administered the University of Pennsylvania Smell Identification Test (UPSIT) and the Picture Identification Test (PIT), a test analogous in content and form to the UPSIT designed to control for non-olfactory cognitive confounds. The UPSIT scores of the myasthenia gravis patients were markedly lower than those of the age- and sex-matched normal controls [respective means (SDs) = 20.15 (6.40) & 35.67 (4.95); p<0.0001], as well as those of the polymiositis patients who scored slightly below the normal range [33.30 (1.42); p<0.0001]. The latter finding, along with direct monitoring of the inhalation of the patients during testing, implies that the MG-related olfactory deficit is unlikely due to difficulties sniffing, per se. All PIT scores were within or near the normal range, although subtle deficits were apparent in both the MG and PM patients, conceivably reflecting influences of mild cognitive impairment. No relationships between performance on the UPSIT and thymectomy, time since diagnosis, type of treatment regimen, or the presence or absence of serum anti-nicotinic or muscarinic antibodies were apparent. Our findings suggest that MG influences olfactory function to the same degree as observed in a number of neurodegenerative diseases in which central nervous system cholinergic dysfunction has been documented. PMID:23082113

  16. Double seronegative myasthenia gravis with antiphospholipid syndrome: a case report

    PubMed Central

    2014-01-01

    Introduction Myasthenia gravis is an autoimmune disease characterized by fluctuating muscle weakness. It is often associated with other autoimmune disorders, such as thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome. Many aspects of autoimmune diseases are not completely understood, particularly when they occur in association, which suggests a common pathogenetic mechanism. Case presentation We report a case of a 42-year-old Caucasian woman with antiphospholipid syndrome, in whom myasthenia gravis developed years later. She tested negative for both antibodies against the acetylcholine receptor and against muscle-specific receptor tyrosine-kinase, but had typical decremental responses at the repetitive nerve stimulation testing, so that a generalized myasthenia gravis was diagnosed. Her thromboplastin time and activated partial thromboplastin time were high, anticardiolipin and anti-β2 glycoprotein-I antibodies were slightly elevated, as a manifestation of the antiphospholipid syndrome. She had a good clinical response when treated with a combination of pyridostigmine, prednisone and azathioprine. Conclusions Many patients with myasthenia gravis test positive for a large variety of auto-antibodies, testifying of an immune dysregulation, and some display mild T-cell lymphopenia associated with hypergammaglobulinemia and B-cell hyper-reactivity. Both of these mechanisms could explain the occurrence of another autoimmune condition, such as antiphospholipid syndrome, but further studies are necessary to shed light on this matter. Clinicians should be aware that patients with an autoimmune diagnosis such as antiphospholipid syndrome who develop signs and neurological symptoms suggestive of myasthenia gravis are at risk and should prompt an emergent evaluation by a specialist. PMID:24380508

  17. Innate immunity in myasthenia gravis thymus: pathogenic effects of Toll-like receptor 4 signaling on autoimmunity.

    PubMed

    Cordiglieri, Chiara; Marolda, Roberta; Franzi, Sara; Cappelletti, Cristina; Giardina, Carmelo; Motta, Teresio; Baggi, Fulvio; Bernasconi, Pia; Mantegazza, Renato; Cavalcante, Paola

    2014-08-01

    The thymus is the main site of immune sensitization to AChR in myasthenia gravis (MG). In our previous studies we demonstrated that Toll-like receptor (TLR) 4 is over-expressed in MG thymuses, suggesting its involvement in altering the thymic microenvironment and favoring autosensitization and autoimmunity maintenance processes, via an effect on local chemokine/cytokine network. Here, we investigated whether TLR4 signaling may favor abnormal cell recruitment in MG thymus via CCL17 and CCL22, two chemokines known to dictate immune cell trafficking in inflamed organs by binding CCR4. We also investigated whether TLR4 activation may contribute to immunodysregulation, via the production of Th17-related cytokines, known to alter effector T cell (Teff)/regulatory T cell (Treg) balance. We found that CCL17, CCL22 and CCR4 were expressed at higher levels in MG compared to normal thymuses. The two chemokines were mainly detected around medullary Hassall's corpuscles (HCs), co-localizing with TLR4(+) thymic epithelial cells (TECs) and CCR4(+) dendritic cells (DCs), that were present in higher number in MG thymuses compared to controls. TLR4 stimulation in MG TECs increased CCL17 and CCL22 expression and induced the production of Th17-related cytokines. Then, to study the effect of TLR4-stimulated TECs on immune cell interactions and Teff activation, we generated an in-vitro imaging model by co-culturing CD4(+) Th1/Th17 AChR-specific T cells, naïve CD4(+)CD25(+) Tregs, DCs and TECs from Lewis rats. We observed that TLR4 stimulation led to a more pronounced Teff activatory status, suggesting that TLR4 signaling in MG thymic milieu may affect cell-to-cell interactions, favoring autoreactive T-cell activation. Altogether our findings suggest a role for TLR4 signaling in driving DC recruitment in MG thymus via CCL17 and CCL22, and in generating an inflammatory response that might compromise Treg function, favoring autoreactive T-cell pathogenic responses. PMID:24397961

  18. Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors — Recommendations for methods and experimental designs

    PubMed Central

    Losen, Mario; Martinez-Martinez, Pilar; Molenaar, Peter C.; Lazaridis, Konstantinos; Tzartos, Socrates; Brenner, Talma; Duan, Rui-Sheng; Luo, Jie; Lindstrom, Jon; Kusner, Linda

    2015-01-01

    Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). This model covers cellular mechanisms involved in the immune response against the AChR, e.g. antigen presentation, T cell-help and regulation, B cell selection and differentiation into plasma cells. Our aim is to define standard operation procedures and recommendations for the rat EAMG model using purified AChR from the Torpedo californica electric organ, in order to facilitate more rapid translation of preclinical proof of concept or efficacy studies into clinical trials and, ultimately, clinical practice. PMID:25796590

  19. [Therapeutic strategies against myasthenia gravis].

    PubMed

    Utsugisawa, Kimiaki; Nagane, Yuriko

    2013-05-01

    Many patients with myasthenia gravis (MG) still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of oral corticosteroids, since full remission is not common. Our analysis demonstrated that disease severity, oral corticosteroids, and depressive state are the major factors negatively associated with QOL, and that QOL of MM status patients taking < or = 5 mg prednisolne/day is identically good as that seen in CSR and is a target of treatment. In order to achieve early MM or better status with prednisolne < or = 5 mg/day, we advocate the early aggressive treatment strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved status using low-dose oral corticosteroids and calcineurin inhibitors. PMID:23777099

  20. Protective molecular mimicry in experimental myasthenia gravis.

    PubMed

    Im, Sin Hyeog; Barchan, Dora; Feferman, Tali; Raveh, Lily; Souroujon, Miriam C; Fuchs, Sara

    2002-05-01

    Protein databases were searched for microbial sequences that bear amino acid similarities with identified T- or B-cell epitopes within the human alpha-subunit of acetylcholine receptor (AChR). One peptide, derived from Haemophilus influenzae, exhibits 50% homology to an identified T-cell epitope of AChR alpha-subunit. This peptide was shown to have a protective effect in experimental autoimmune myasthenia gravis (EAMG). Pretreatment of rats with the mimicry peptide attenuated the induction and progression of EAMG. These effects were accompanied by a reduced T-cell response to AChR, diminished IL-2, IL-12, IFN-gamma and IL-4 levels, as well as decreased humoral response to self-AChR. PMID:12020961

  1. Impaired regulatory B cells in myasthenia gravis.

    PubMed

    Sheng, Jian Rong; Rezania, Kourosh; Soliven, Betty

    2016-08-15

    Regulatory B cells (Bregs) attenuate the severity of experimental autoimmune myasthenia gravis (EAMG) in an interleukin-10 (IL-10)-dependent manner. The goal of this study was to investigate the role of human Bregs in MG focusing on CD19(+)CD1d(hi) CD5(+) and CD19(+)CD24(hi)CD38(hi) subsets. We found that MG patients exhibited a decrease in the frequency of both Breg subsets and IL-10 producing B cells within each subset, which correlated with disease severity. In addition, there was impaired suppression of Th1 polarization in MG. These findings, taken together with EAMG data, indicate that Bregs play an important role in regulating the severity of MG. PMID:27397074

  2. Myasthenia gravis: past, present, and future

    PubMed Central

    Conti-Fine, Bianca M.; Milani, Monica; Kaminski, Henry J.

    2006-01-01

    Myasthenia gravis (MG) is an autoimmune syndrome caused by the failure of neuromuscular transmission, which results from the binding of autoantibodies to proteins involved in signaling at the neuromuscular junction (NMJ). These proteins include the nicotinic AChR or, less frequently, a muscle-specific tyrosine kinase (MuSK) involved in AChR clustering. Much is known about the mechanisms that maintain self tolerance and modulate anti-AChR Ab synthesis, AChR clustering, and AChR function as well as those that cause neuromuscular transmission failure upon Ab binding. This insight has led to the development of improved diagnostic methods and to the design of specific immunosuppressive or immunomodulatory treatments. PMID:17080188

  3. Congenital myasthenic syndromes and transient myasthenia gravis.

    PubMed

    Gajda, Anna; Szabó, Hajnalka; Gergev, Gyurgyinka; Karcagi, Veronika; Szabó, Nóra; Endreffy, Emoke; Túri, Sándor; Sztriha, László

    2013-05-30

    Hypotonia in the neonatal period and early infancy is a common clinical finding. It can be caused by various heterogeneous disorders of different origin which might lead to diagnostic difficulties. Disorders of the neuromuscular junction, such as congenital myasthenic syndromes and neonatal transient myasthenia gravis are among the aetiologies. We report on a case of congenital myasthenia caused by mutation in the long cytoplasmic loop of the epsilon subunit of the acetylcholine receptor and a neonate of a myasthenic mother diagnosed with transient myasthenia gravis. PMID:23909021

  4. Sensory aspects in myasthenia gravis: A translational approach.

    PubMed

    Leon-Sarmiento, Fidias E; Leon-Ariza, Juan S; Prada, Diddier; Leon-Ariza, Daniel S; Rizzo-Sierra, Carlos V

    2016-09-15

    Myasthenia gravis is a paradigmatic muscle disorder characterized by abnormal fatigue and muscle weakness that worsens with activities and improves with rest. Clinical and research studies done on nicotinic acetylcholine receptors have advanced our knowledge of the muscle involvement in myasthenia. Current views still state that sensory deficits are not "features of myasthenia gravis". This article discusses the gap that exists on sensory neural transmission in myasthenia that has remained after >300years of research in this neurological disorder. We outline the neurobiological characteristics of sensory and motor synapses, reinterpret the nanocholinergic commonalities that exist in both sensory and motor pathways, discuss the clinical findings on altered sensory pathways in myasthenia, and propose a novel way to score anomalies resulting from multineuronal inability associated sensory troubles due to eugenic nanocholinergic instability and autoimmunity. This medicine-based evidence could serve as a template to further identify novel targets for studying new medications that may offer a better therapeutic benefit in both sensory and motor dysfunction for patients. Importantly, this review may help to re-orient current practices in myasthenia. PMID:27538668

  5. Specific Immunotherapy of Experimental Myasthenia Gravis by A Novel Mechanism

    PubMed Central

    Luo, Jie; Kuryatov, Alexander; Lindstrom, Jon

    2009-01-01

    Objective Myasthenia gravis (MG) and its animal model, experimental autoimmune myasthenia gravis (EAMG), are antibody-mediated autoimmune diseases, in which autoantibodies bind to and cause loss of muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. To develop a specific immunotherapy of MG, we treated rats with ongoing EAMG by intraperitoneal injection of bacterially-expressed human muscle AChR constructs. Methods Rats with ongoing EAMG received intraperitoneal treatment with the constructs weekly for 5 weeks beginning after the acute phase. Autoantibody concentration, subclassification, and specificity were analyzed to address underlying therapeutic mechanism. Results EAMG was specifically suppressed by diverting autoantibody production away from pathologically relevant specificities directed at epitopes on the extracellular surface of muscle AChRs toward pathologically irrelevant epitopes on the cytoplasmic domain. A mixture of subunit cytoplasmic domains was more effective than a mixture containing both extracellular and cytoplasmic domains or than only the extracellular domain of α1 subunits. Interpretation Therapy using only cytoplasmic domains, which lack pathologically relevant epitopes, avoids the potential liability of boosting the pathological response. Use of a mixture of bacterially-expressed human muscle AChR cytoplasmic domains for antigen-specific immunosuppression of myasthenia gravis has the potential to be specific, robust, and safe. PMID:20437579

  6. Association of myasthenia gravis and Behçet's disease: A case report.

    PubMed

    Kisabay, Aysin; Sari, Ummu Serpil; Boyaci, Recep; Batum, Melike; Yilmaz, Hikmet; Selcuki, Deniz

    2016-01-01

    Myasthenia gravis is a disease of neuromuscular junction due to auto-immune destruction of the acetylcholine receptors. Behçet's disease, on the other hand, is a multisystemic vascular-inflammatory disease. Both conditions are not common in the general population although their association has not been reported in the literature. We wanted to present our patient who developed clinical course of myasthenia gravis following discontinuation of medications due to complications of corticosteroid for Behçet's disease. It was observed that clinical findings of myasthenia gravis recovered following restarting steroid treatment and he did not experience attacks of both conditions. Although Myasthenia gravis and Behçet's disease are distinct entities clinically as well as in terms of pathogenesis, they share common physiopathological features and their treatment is based on their common features. PMID:27375145

  7. The potential role of cell surface complement regulators and circulating CD4+ CD25+ T-cells in the development of autoimmune myasthenia gravis

    PubMed Central

    Hamdoon, Mohamed Nasreldin Thabit; Fattouh, Mona; El-din, Asmaa Nasr; Elnady, Hassan M.

    2016-01-01

    Introduction CD4+CD25+ regulatory T-lymphocytes (T-regs) and regulators of complement activity (RCA) involving CD55 and CD59 play an important role in the prevention of autoimmune diseases. However, their role in the pathogenesis of human autoimmune myasthenia gravis (MG) remains unclear. This study aimed to determine the frequency of peripheral blood T-regs and CD4+ T-helper (T-helper) cells and the red blood cells (RBCs) level of expression of CD55 and CD59 in MG patients. Methods Fourteen patients with MG in neurology outpatient clinics of Sohag University Hospital and Sohag General Hospital from March 2014 to December 2014, and 10 age-matched healthy controls participated in this case-control study. We did flowcytometric assessments of the percentage of peripheral T-regs and T-helper cells and the level of expression of CD55 and CD59 on RBCs in the peripheral blood of patients and controls. Results There was a statistically significant decrease in the percentage of peripheral blood T-regs and T-regs/T-helper cell ratio in the MG patients group. Moreover, the level of expression of CD55, CD59, and dual expression of CD55/CD59 on RBCs were statistically significantly lower in MG patients than those of healthy controls. However, regression analysis indicated that there was no significant correlation between all the measured parameters and disease duration or staging. Conclusion Functional defects in the T-regs and RCA may play a role in the pathogenesis of autoimmune MG and their functional modulation may represent an alternative therapeutic strategy for MG treatment. PMID:26955441

  8. Deficits in Endogenous Adenosine Formation by Ecto-5′-Nucleotidase/CD73 Impair Neuromuscular Transmission and Immune Competence in Experimental Autoimmune Myasthenia Gravis

    PubMed Central

    Cristina Costa, Ana; Guerra-Gomes, Sónia; Ferreirinha, Fátima; Magalhães-Cardoso, Maria Teresa; Correia-de-Sá, Paulo

    2015-01-01

    AMP dephosphorylation via ecto-5′-nucleotidase/CD73 is the rate limiting step to generate extracellular adenosine (ADO) from released adenine nucleotides. ADO, via A2A receptors (A2ARs), is a potent modulator of neuromuscular and immunological responses. The pivotal role of ecto-5′-nucleotidase/CD73, in controlling extracellular ADO formation, prompted us to investigate its role in a rat model of experimental autoimmune myasthenia gravis (EAMG). Results show that CD4+CD25+FoxP3+ regulatory T cells express lower amounts of ecto-5′-nucleotidase/CD73 as compared to controls. Reduction of endogenous ADO formation might explain why proliferation of CD4+ T cells failed upon blocking A2A receptors activation with ZM241385 or adenosine deaminase in EAMG animals. Deficits in ADO also contribute to neuromuscular transmission failure in EAMG rats. Rehabilitation of A2AR-mediated immune suppression and facilitation of transmitter release were observed by incubating the cells with the nucleoside precursor, AMP. These findings, together with the characteristic increase in serum adenosine deaminase activity of MG patients, strengthen our hypothesis that the adenosinergic pathway may be dysfunctional in EAMG. Given that endogenous ADO formation is balanced by ecto-5′-nucleotidase/CD73 activity and that A2ARs exert a dual role to restore use-dependent neurocompetence and immune suppression in myasthenics, we hypothesize that stimulation of the two mechanisms may have therapeutic potential in MG. PMID:25691808

  9. Reversible man-in-the-barrel syndrome in myasthenia gravis

    PubMed Central

    Shah, Poornima A; Wadia, Pettarusp Murzban

    2016-01-01

    Man-in-the-barrel syndrome (MBS) is an uncommon presentation due to bilateral, predominantly proximal muscle weakness that has not been described to be associated with myasthenia gravis. We describe a case of myasthenia gravis presenting as MBS. Additionally, he had significant wasting of the deltoids bilaterally with fibrillations on electromyography (EMG) at rest and brief duration (3-6 ms) bi/triphasic motor unit potentials (MUPs) on submaximal effort apart from a decremental response on repetitive nerve stimulation (RNS) at 2 Hz. While electrophysiology is an important tool in the diagnosis of myasthenia gravis, pathological EMG patterns do not exclude the diagnosis of myasthenia gravis. PMID:27011638

  10. Unusual association of amyotrophic lateral sclerosis and myasthenia gravis: A dysregulation of the adaptive immune system?

    PubMed

    Del Mar Amador, Maria; Vandenberghe, Nadia; Berhoune, Nawel; Camdessanché, Jean-Philippe; Gronier, Sophie; Delmont, Emilien; Desnuelle, Claude; Cintas, Pascal; Pittion, Sophie; Louis, Sarah; Demeret, Sophie; Lenglet, Timothée; Meininger, Vincent; Salachas, François; Pradat, Pierre-François; Bruneteau, Gaëlle

    2016-06-01

    Myasthenia gravis is an autoimmune disorder affecting neuromuscular junctions that has been associated with a small increased risk of amyotrophic lateral sclerosis (ALS). Here, we describe a retrospective series of seven cases with a concomitant diagnosis of ALS and myasthenia gravis, collected among the 18 French reference centers for ALS in a twelve year period. After careful review, only six patients strictly met the diagnostic criteria for both ALS and myasthenia gravis. In these patients, limb onset of ALS was reported in five (83%) cases. Localization of myasthenia gravis initial symptoms was ocular in three (50%) cases, generalized in two (33%) and bulbar in one (17%). Median delay between onset of the two conditions was 19 months (6-319 months). Anti-acetylcholine receptor antibodies testing was positive in all cases. All patients were treated with riluzole and one had an associated immune-mediated disease. In the one last ALS case, the final diagnosis was false-positivity for anti-acetylcholine receptor antibodies. The co-occurrence of ALS and myasthenia gravis is rare and requires strict diagnostic criteria. Its demonstration needs thoughtful interpretation of electrophysiological results and exclusion of false positivity for myasthenia gravis antibody testing in some ALS cases. This association may be triggered by a dysfunction of adaptive immunity. PMID:27102004

  11. IL-17-producing CD4(+) T cells contribute to the loss of B-cell tolerance in experimental autoimmune myasthenia gravis.

    PubMed

    Schaffert, Hanne; Pelz, Andreas; Saxena, Abhishek; Losen, Mario; Meisel, Andreas; Thiel, Andreas; Kohler, Siegfried

    2015-05-01

    The role of Th17 cells in the pathogenesis of autoantibody-mediated diseases is unclear. Here, we assessed the contribution of Th17 cells to the pathogenesis of experimental autoimmune myasthenia gravis (EAMG), which is induced by repetitive immunizations with Torpedo californica acetylcholine receptor (tAChR). We show that a significant fraction of tAChR-specific CD4(+) T cells is producing IL-17. IL-17(ko) mice developed fewer or no EAMG symptoms, although the frequencies of tAChR-specific CD4(+) T cells secreting IL-2, IFN-γ, or IL-21, and the percentage of FoxP3(+) Treg cells were similar to WT mice. Even though the total anti-tAChR antibody levels were equal, the complement fixating IgG2b subtype was reduced in IL-17(ko) as compared to WT mice. Most importantly, pathogenic anti-murine AChR antibodies were significantly lower in IL-17(ko) mice. Furthermore, we confirmed the role of Th17 cells in EAMG pathogenesis by the reconstitution of TCR β/δ(ko) mice with WT or IL-17(ko) CD4(+) T cells. In conclusion, we show that the level of IgG2b and the loss of B-cell tolerance, which results in pathogenic anti-murine AChR-specific antibodies, are dependent on IL-17 production by CD4(+) T cells. Thus, we describe here for the first time how Th17 cells are involved in the induction of classical antibody-mediated autoimmunity. PMID:25676041

  12. A study of the utility of azathioprine metabolite testing in myasthenia gravis.

    PubMed

    Rae, William; Burke, Georgina; Pinto, Ashwin

    2016-04-15

    Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterised by fatigable voluntary skeletal muscle weakness. The underlying pathogenesis is complex involving adaptive autoimmune responses. Azathioprine remains a first line broad acting immunosuppressant for MG. Due to varied clinical responses to azathioprine we aimed to investigate the relationship between azathioprine metabolites and symptom control. Mild correlations between Quantitative Myasthenia Gravis Score (QMG) vs. 6-thioguanine nucleotides (R=-0.317 p=0.186) and QMG vs. lymphocyte count (R=0.402 p=0.08) were found. Azathioprine metabolite measurement should be considered in MG patients with; pancytopenia, deranged liver function or recurrent infections. PMID:27049566

  13. Myasthenia gravis treated with purified antithymocyte antiserum.

    PubMed

    Pirofsky, B; Reid, R H; Bardana, E J; Baker, R L

    1979-01-01

    The therapeutic effect of goat anti-human thymocyte antiserum globulin (ATG) was assessed in 10 patients with myasthenia gravis. All subjects had far-advanced, debilitating disease poorly responsive to anticholinesterase therapy. Prolonged, low-dose ATG therapy was used, with 1.0 to 2.6 gm ATG protein administered intramuscularly over a 28- to 73-day period. Therapeutic responses of varying degrees were noted in 8 of 10 patients. Completion of a course of ATG treatment and discontinuation of the drug did not lead to acute relapse. Follow-up examinations for over 5 years have been maintained. A mean remission period of approximately 2 years was observed. This therapy deserves further evaluation; subjects with progressive myasthenia gravis despite prior thymectomy may represent ideal candidates. PMID:311448

  14. Prediction of aspiration in myasthenia gravis.

    PubMed

    Koopman, Wilma J; Wiebe, Samuel; Colton-Hudson, Angela; Moosa, Tas; Smith, Dean; Bach, David; Nicolle, Michael W

    2004-02-01

    Prediction of the risk of dysphagia and aspiration is important in the management of myasthenia gravis (MG). We assessed the ability of four bedside clinical tools to predict aspiration in 20 MG patients. Patients completed a self-directed questionnaire, underwent clinical neurological assessment and a bedside speech pathology assessment, and were assessed with the quantitative myasthenia gravis (QMG) score. The ability of these tools to predict aspiration was compared with the results of a modified barium swallow. Seven patients aspirated, 4 silently. The total self-directed questionnaire score, two specific questions on the self-directed questionnaire, the prediction based on clinical neurological assessment, and the QMG bulbar subset score all correlated with aspiration. The speech pathology prediction was highly sensitive but less specific. This pilot study shows that simple clinical tools can predict which MG patients are at risk of aspiration. PMID:14755491

  15. Emergency Management of Myasthenia Gravis

    MedlinePlus

    ... head and shoulders. • Keep a calm and peaceful atmosphere. • Support respirations if needed. SEVERE SWALLOWING DIFFICULTY Subjective ... secretions as needed. • Keep a calm and peaceful atmosphere. www.myasthenia.org 800.541.5454

  16. Epidemiology of myasthenia gravis in Ontario, Canada.

    PubMed

    Breiner, Ari; Widdifield, Jessica; Katzberg, Hans D; Barnett, Carolina; Bril, Vera; Tu, Karen

    2016-01-01

    Incidence and prevalence estimates in myasthenia gravis have varied widely. Recent studies based on administrative health data have large sample sizes but lack rigorous validation of MG cases, and have not examined the North American population. Our aim was to explore trends in MG incidence and prevalence for the years 1996-2013 in the province of Ontario, Canada (population 13.5 million). We employed a previously validated algorithm to identify MG cases. Linking with census data allowed for the calculation of crude- and age/sex-standardized incidence and prevalence rates for the years 1996-2013. The regional distribution of MG cases throughout the province was examined. Mean age at the first myasthenia gravis encounter was 60.2 ± 17.1 years. In 2013, there were 3611 prevalent cases in Ontario, and the crude prevalence rate was 32.0/100,000 population. Age- and sex-standardized prevalence rates rose consistently over time from 16.3/100,000 (15.4-17.1) in 1996 to 26.3/100,000 (25.4-27.3) in 2013. Standardized incidence rates remained stable between 1996 (2.7/100,000; 95% CL 2.3-3.0) and 2013 (2.3/100,000; 2.1-2.6). Incidence was highest in younger women and older men, and geographic variation was evident throughout the province. In conclusion, this large epidemiological study shows rising myasthenia gravis prevalence with stable incidence over time, which is likely reflective of patients living longer, possibly due to improved disease treatment. Our findings provide accurate information on the Canadian epidemiology of myasthenia gravis and burden for health care resources planning for the province, respectively. PMID:26573434

  17. Ocular Myasthenia Gravis Associated With Thymic Amyloidosis.

    PubMed

    Chapman, Kristin O; Beneck, Debra M; Dinkin, Marc J

    2016-03-01

    A 45-year-old woman with ptosis and diplopia was found to have myasthenia gravis (MG) associated with amyloidosis of the thymus gland. Systemic MG is frequently associated with thymomas or thymic hyperplasia but has only once previously been reported in association with amyloidosis of the thymus. This case demonstrates that isolated ocular MG rarely may also be associated with amyloidosis of the thymus. PMID:25822660

  18. Effectiveness of steroid treatment in myasthenia gravis: a retrospective study.

    PubMed

    Cosi, V; Citterio, A; Lombardi, M; Piccolo, G; Romani, A; Erbetta, A

    1991-07-01

    The records of 142 patients with generalized autoimmune myasthenia gravis who had been treated with steroids as the single immunosuppressive agent, collected at regular intervals, were employed for a retrospective evaluation. The effectiveness of treatment was assessed after 24 months; the data from the 6th and 12th months were also considered. After 24 months, 63.4% of the whole sample had improved (33.8% were in clinical or pharmacological remission); 13.4% were unchanged or had worsened and 22.3% had moved to a different immunosuppressive treatment. The rate of positive outcome was higher in patients over the age of 40 at disease onset. PMID:1927259

  19. Acupuncture anesthesia in thymectomy on myasthenia gravis patients.

    PubMed

    Dong, S T; Nguyen, V T; Nguyen, V T; Vu, T A; Pham, M H

    1988-01-01

    Thymectomy is often successful as treatment for the autoimmune disease myasthenia gravis. One complication of the operation on such patients is respiratory difficulty especially post-operatively, due to interference with the already disturbed transmission of signals along damaged nerve-endings. Acupuncture anesthesia offers a solution to that problem. In this series of 90 patients, the results of operation under conventional general anesthesia were compared with those under acupuncture anesthesia. It was found that patients in the latter group suffered fewer complications. PMID:2898196

  20. Myasthenia gravis and masticatory muscle myositis in a dog

    PubMed Central

    Clooten, Jennifer K.; Woods, J. P.; Smith-Maxie, Laura L.

    2003-01-01

    A 21-month-old, castrated male Vizsla was presented for pelvic limb weakness, difficulty opening his mouth, ptyalism, voice change, and urinary incontinence. Myasthenia gravis and masticatory myositis were diagnosed. The unusual clinical findings, diagnosis, treatment, and case outcome are described, followed by a brief discussion of myasthenia gravis and masticatory myositis. PMID:12839242

  1. Steroids induce acetylcholine receptors on cultured human muscle: Implications for myasthenia gravis

    SciTech Connect

    Kaplan, I.; Blakely, B.T.; Pavlath, G.K.; Travis, M.; Blau, H.M. )

    1990-10-01

    Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. The authors show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. The results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also a direct effect on muscle. They propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications.

  2. Treatment of experimental myasthenia gravis with total lymphoid irradiation

    SciTech Connect

    de Silva, S.; Blum, J.E.; McIntosh, K.R.; Order, S.; Drachman, D.B.

    1988-07-01

    Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented the primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis.

  3. Development of myasthenia gravis after interferon alpha therapy.

    PubMed

    Gurtubay, I G; Morales, G; Aréchaga, O; Gállego, J

    1999-03-01

    Interferon (IFN) alpha is now used in the treatment of some malignant diseases and chronic viral hepatitis. There have been several reports of development of autoantibodies and autoimmune diseases or the deterioration of preexisting disorders in patients under treatment. We enclose a case of myasthenia gravis (MG) which developed after six weeks of treatment as fluctuating bilateral ptosis, intermittent diplopia, and mild weakness of limb and neck muscles. A test dose of edrophonium chloride was administered, resulting in improved muscle strength. Elevated anti acetylcholine receptor (AChR) antibody titer was found. Single fiber electromyography showed an increased jitter from extensor digitorum communis, frequently accompanied by transmission blocking. Repetitive electric 3 Hz stimulation of the abductor pollicis brevis muscle, revealed an abnormal decrement of 28% in compound motor action potential. Myasthenia gravis was diagnosed and the patient was given pyridostigmine, immunoglobulines and prednisone with benefit. Six months latter he developed an acute myasthenic crisis with severe respiratory failure and high anti AChR antibody titer. IFN-alpha can induce MG or simply manifests a preexisting subclinical disease, but otherwise its therapeutic efficacy in MG has been shown in experimental and clinical studies. Autoimmune mechanisms, as the release of different cytokines as IFN, by immunocompetent cells, may be involved in the pathogenesis of both MG and chronic active hepatitis. Autoantibody production against postsynaptic membrane structures by IFN-alpha could be the underlying pathophysiology. PMID:10207675

  4. Immunological relationship between acetylcholine receptor and thymus: a possible significance in myasthenia gravis.

    PubMed Central

    Aharonov, A; Tarrab-Hazdai, R; Abramsky, O; Fuchs, S

    1975-01-01

    A defined immunological cross-reaction was observed between acetylcholine receptor fraction from the electric eel, Electrophorus electricus, and two calf thymus fractions. The cross-reaction was demonstrated on the cellular level by means of the lymphocyte transformation technique, and on the humoral level, by means of the microcomplement fixation assay. In the human disease myasthenia gravis both acetylcholine receptor at the neuromuscular junction and the thymus are affected, probably by an autoimmune mechanism. The immunological cross-reaction between acetylcholine receptor and thymic components may explain the association between endplate and thymus disorders in myasthenia gravis. PMID:1055418

  5. Caudal epidural anesthesia for a 2-year old child with congenital myasthenia gravis.

    PubMed

    Calişkan, Esra; Koçum, Aysu; Sener, Mesut; Bozdoğan, Nesrin; Ariboğan, Aniş

    2008-10-01

    Myasthenia gravis is an autoimmune disease with antibodies directed against the acetylcholine receptor at the neuromuscular junction. Anesthetists have a special interest in myasthenia gravis because of its interaction with various anesthetic agents. Unlike adult myasthenic patients; very little report has been written about the anesthetic management in children, other than in relation to thymectomy. Although the use of caudal anesthesia in pediatric patients is common, have not seen any report concerning its use in a myasthenic child. In this case report, we represented a 2 year-old boy was performed caudal anesthesia for orchiopexy operation. He had presented difficulty in breathing, generalized weakness and droopy eyes due to congenital myasthenia gravis. In the operating room, following the routine monitoring, the patient was sedated with intravenous 1mg midazolam and 10 mg ketamine. Then caudal block was performed. 17 minutes later from the local anesthetic injection; operation was started and lasted 45 minutes. The patient did not require intraoperative supplemental analgesia and postoperative course was uneventful. Specific attention should be paid to voluntary and respiratory muscle strength in myasthenia gravis patients. Caudal anesthesia allowed airway control of myasthenia gravis patients without endotracheal intubations and muscle relaxant. In conclusion, we think that caudal anesthetic technique may be considered as a safe and suitable for the myasthenic child and it may represent a valid alternative to general anesthesia for these patients. PMID:19117157

  6. Myasthenia gravis: a careful perioperative anesthetic management of coronary artery bypass grafting.

    PubMed

    Kowalczyk, Michał; Nestorowicz, Andrzej; Stachurska, Katarzyna; Fijałkowska, Anna; Stążka, Janusz

    2015-06-01

    Nowadays, even hazardous cardiac surgery can be performed on patients with autoimmune diseases like myasthenia gravis. It requires a sensitive perioperative anesthetic approach especially in relation to nondepolarizing muscle relaxant administration. Myasthenic patients produce antibodies against the end-plate acetylcholine receptors causing muscle weakness and sensitivity to nondepolarizing muscle relaxants that could lead to respiratory failure. Perioperative nurse care is critical for uncomplicated course of treatment; therefore, apprehension of surgical procedure should be helpful on an everyday basis. We describe successful management without any pulmonary complications of two patients with myasthenia gravis undergoing coronary artery bypass grafting. In addition, antiacetylcholine receptor antibodies concentrations were evaluated during treatment time. In conclusion, we have found that reduced titrated doses of cisatracurium may be safely used in patients with myasthenia gravis undergoing cardiac surgery without anesthesia and respiratory-related complications. PMID:25943997

  7. A sodium channel myotonia due to a novel SCN4A mutation accompanied by acquired autoimmune myasthenia gravis.

    PubMed

    Kokunai, Yosuke; Goto, Keigo; Kubota, Tomoya; Fukuoka, Takaaki; Sakoda, Saburo; Ibi, Tohru; Doyu, Manabu; Mochizuki, Hideki; Sahashi, Ko; Takahashi, Masanori P

    2012-06-21

    Mutations of the voltage gated sodium channel gene (SCN4A) are responsible for non-dystrophic myotonia including hyperkalemic periodic paralysis, paramyotonia congenita, and sodium channel myotonia, as well as congenital myasthenic syndrome. In vitro functional analyses have demonstrated the non-dystrophic mutants to show a gain-of-function defect of the channel; a disruption of fast inactivation, an enhancement of activation, or both, while the myasthenic mutation presents a loss-of function defect. This report presents a case of non-dystrophic myotonia that is incidentally accompanied with acquired myasthenia. The patient presented a marked warm-up phenomenon of myotonia but the repeated short exercise test suggested mutations of the sodium channel. The genetic analysis identified a novel mutation, G1292D, of SCN4A. A functional study of the mutant channel revealed marked enhancement of activation and slight impairment of fast inactivation, which should induce muscle hyperexcitability. The effects of the alteration of channel function to the myasthenic symptoms were explored by using stimulation of repetitive depolarization pulses. A use-dependent channel inactivation was reduced in the mutant in comparison to normal channel, thus suggesting an opposing effect to myasthenia. PMID:22617007

  8. Myasthenia gravis and related disorders: Pathology and molecular pathogenesis.

    PubMed

    Ha, James C; Richman, David P

    2015-04-01

    Disorders affecting the presynaptic, synaptic, and postsynaptic portions of the neuromuscular junction arise from various mechanisms in children and adults, including acquired autoimmune or toxic processes as well as genetic mutations. Disorders include autoimmune myasthenia gravis associated with acetylcholine receptor, muscle specific kinase or Lrp4 antibodies, Lambert-Eaton myasthenic syndrome, nerve terminal hyperexcitability syndromes, Guillain Barré syndrome, botulism, organophosphate poisoning and a number of congenital myasthenic syndromes. This review focuses on the various molecular and pathophysiological mechanisms of these disorders, characterization of which has been crucial to the development of treatment strategies specific for each pathogenic mechanism. In the future, further understanding of the underlying processes may lead to more effective and targeted therapies of these disorders. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. PMID:25486268

  9. Animal models of myasthenia gravis: utility and limitations

    PubMed Central

    Mantegazza, Renato; Cordiglieri, Chiara; Consonni, Alessandra; Baggi, Fulvio

    2016-01-01

    Myasthenia gravis (MG) is a chronic autoimmune disease caused by the immune attack of the neuromuscular junction. Antibodies directed against the acetylcholine receptor (AChR) induce receptor degradation, complement cascade activation, and postsynaptic membrane destruction, resulting in functional reduction in AChR availability. Besides anti-AChR antibodies, other autoantibodies are known to play pathogenic roles in MG. The experimental autoimmune MG (EAMG) models have been of great help over the years in understanding the pathophysiological role of specific autoantibodies and T helper lymphocytes and in suggesting new therapies for prevention and modulation of the ongoing disease. EAMG can be induced in mice and rats of susceptible strains that show clinical symptoms mimicking the human disease. EAMG models are helpful for studying both the muscle and the immune compartments to evaluate new treatment perspectives. In this review, we concentrate on recent findings on EAMG models, focusing on their utility and limitations. PMID:27019601

  10. Ocular myasthenia gravis accompanied by anosmia.

    PubMed

    Chen, Ying; Wang, Li; Zhou, Li; Gao, Ying

    2016-02-01

    We report a case of ocular myasthenia gravis (MG) accompanied by anosmia. A 76-year-old man had idiopathic anosmia of 2-year duration. Four months before consultation, he began to have drooping in the right upper eyelid along with muscle soreness, distension, and pain in the nape. His tongue was dark-red with a thin and white coating; his pulse was wiry and slippery. According to Traditional Chinese Medicine, eyelid drooping and anosmia are the main signs of liver constraint and spleen deficiency. In Western Medicine, the diagnosis was ocular MG and idiopathic anosmia. Our patient, along with the literature, suggests that anosmia may be an early symptom before MG. MG accompanied by anosmia could be a special subtype of MG according to antibody production and symptoms. PMID:26946629

  11. Myasthenia Gravis and the Myasthenic Syndrome

    PubMed Central

    Herrmann, Christian

    1970-01-01

    Two disorders of neuromuscular transmission producing muscle weakness and easy fatigability which may confront the physician are myasthenia gravis and the myasthenic syndrome. The former has early symptoms and signs of oculobulbar and then extremity weakness with rapid decline of action potential and contractile strength with repetitive use and nerve-muscle stimulation. Anticholinesterases improve strength. The myasthenic syndrome has early symptoms and signs of pelvic girdle, pectoral girdle and proximal limb muscle weakness. This is worst when first starting to use or carry out nerve muscle stimulation in the rested muscles. It improves significantly for a time with use or on rapid stimulation, and then declines with continued activation. Deep tendon reflexes are sluggish or absent. Small cell carcinoma of the lung is often associated. Guanidine improves the strength. Other features and possible underlying mechanisms of the two disorders help to differentiate and treat them. PMID:5457513

  12. Myasthenia gravis and invasive thymoma with multiple intracranial metastases.

    PubMed

    Koç, Filiz; Yerdelen, Deniz; Sarica, Yakup

    2003-06-01

    Myasthenia gravis (MG) is an autoimmune disease. Approximately 15% of patients with MG have thymoma. Approximately 30% to 40% of them are invasive. A 26-year-old man was admitted with cough and difficulty breathing. He had transsternal thymectomy resulting from MG accompanied by thymoma 6 years previously. Thorax computerized tomography (CT) scans showed metastases to the extra-mediastinum. Diagnosis of invasive thymoma was made by CT-guided biopsy. A PAC regimen (cisplatin, doxorubicin, cyclophosphamide) and radiotherapy were added to MG treatment. Ten months later, he presented again with headache, weakness, and difficulty swallowing. We determined that he had intracranial multiple metastases. He was hospitalized. Cerebral multiple metastases were evaluated as inoperable. However, he died of transtentorial herniation after 1 month. This MG case accompanied by invasive thymoma with multiple intracranial metastases is discussed. PMID:19078711

  13. Neuromyelitis optica and myasthenia gravis in a young Nigerian girl.

    PubMed

    Balarabe, Salisu Abdullahi; Adamu, Mohammad Dantani; Watila, Musa Mamman; Jiya, Nma

    2015-01-01

    Neuromyelitis optica (NMO) and myasthenia gravis (MG) are rare autoimmune disorders. The coexistence of the two disorders, although rare, has been documented. This is a case report of a 16-year-old student who presented with recurrent episodes of transverse myelitis and optic neuritis, 8 years after diagnosis of MG. She presented with visual impairment, relapsing and remitting weakness, numbness and paraesthesia of her lower limbs, with bladder and bowel incontinence. Her examination revealed bilateral optic atrophy, spastic paraparesis of the lower limbs and patchy sensory loss up to thoracic level (T4-5). She had a positive acetylcholine receptor antibody, a positive aquaporin-4 antibody and chest CT finding of thymic enlargement. We therefore confirmed the previous diagnosis of MG and performed a recent diagnosis of background NMO. A high index of suspicion is needed to make a diagnosis of this rare coexistence of NMO and MG in resource-limited settings such as Nigeria. PMID:26338241

  14. Idiopathic Pulmonary Fibrosis and Myasthenia Gravis: An Unusual Association

    PubMed Central

    Chogtu, Bharti; Malik, Daliparty Vasudev

    2016-01-01

    Idiopathic Pulmonary Fibrosis (IPF) is a chronic fibrosing lung condition with high morbidity and mortality, accounting for about 25% of the cases of interstitial lung diseases. It usually has a progressive course resulting in death due to respiratory failure. Myasthenia Gravis (MG) is an autoimmune neuromuscular disease, caused by antibody mediated activity against acetylcholine receptor at the neuromuscular junction. It is characterized by fluctuating muscle weakness and fatigue. Extensive literature search did not reveal any case report of an association between these two conditions. Here we present a case of a patient with IPF who also developed MG. The diagnosis of IPF was based on High Resolution Computed Tomography (HRCT) of the lung and that of MG was based on clinical criteria and electrophysiological testing. The case was successfully managed. PMID:27190866

  15. Idiopathic Pulmonary Fibrosis and Myasthenia Gravis: An Unusual Association.

    PubMed

    Chogtu, Bharti; Malik, Daliparty Vasudev; Magazine, Rahul

    2016-04-01

    Idiopathic Pulmonary Fibrosis (IPF) is a chronic fibrosing lung condition with high morbidity and mortality, accounting for about 25% of the cases of interstitial lung diseases. It usually has a progressive course resulting in death due to respiratory failure. Myasthenia Gravis (MG) is an autoimmune neuromuscular disease, caused by antibody mediated activity against acetylcholine receptor at the neuromuscular junction. It is characterized by fluctuating muscle weakness and fatigue. Extensive literature search did not reveal any case report of an association between these two conditions. Here we present a case of a patient with IPF who also developed MG. The diagnosis of IPF was based on High Resolution Computed Tomography (HRCT) of the lung and that of MG was based on clinical criteria and electrophysiological testing. The case was successfully managed. PMID:27190866

  16. Genetic basis of myasthenia gravis - a comprehensive review.

    PubMed

    Avidan, Nili; Le Panse, Rozen; Berrih-Aknin, Sonia; Miller, Ariel

    2014-08-01

    Myasthenia gravis (MG) is a rare autoimmune disease characterized by the production of autoantibodies against proteins of the postsynaptic membrane in the neuromuscular junction. The estimated number of MG patients is steadily increasing, and it had more than doubled in the last 20 years. Monozygotic MG twin concordance is estimated to be about 35% supporting the central role of environmental factors in MG etiology. Epigenetics, presume to be the mechanistic link between environmental and genetic risk factors in disease development, provides support for specific microRNAs associated with MG. Genetic studies have mainly pointed at specific HLA alleles implicated in MG susceptibility, however recently both TNFAIP3-interacting protein 1 (TNIP1) and tyrosine phosphatase non-receptor 22 (PTPN22) were indicated to be associated with MG in a GWAS study. A gender bias was observed for SNPs in the HLA-locus, suggesting female-specific alleles have an increase risk for MG. Moreover, sex hormones play a pivotal role in the gender bias in autoimmunity in general and in MG in particular. Hence the genetic basis of gender bias might be highly pertinent to MG and deserves further characterization. Pathway-based analyses that combine information across multiple genes into a limited number of molecular networks have been found to be a powerful approach. Both regulatory T-cell (Treg) differentiation and NF-κB signaling pathway have been shown to have relevance to MG pathophysiology. Hence studies centered around two pathways might be a fruitful approach to identify additional polymorphisms associated with myasthenia gravis. PMID:24361103

  17. Inhibitory effect of alpha-fetoprotein on the binding of myasthenia gravis antibody to acetylcholine receptor.

    PubMed Central

    Brenner, T; Beyth, Y; Abramsky, O

    1980-01-01

    The binding of myasthenia gravis antibody acetylcholine receptor (AcChoR) as measured in vitro by Radioimmunoassay with 125I-labeled alpha-bungarotoxin (alpha-BuTx), can be blocked by amniotic fluid, maternal serum, and umbilical cord serum. This inhibitory effect is due to alpha-fetoprotein present in high concentrations in amniotic fluid and serum, as shown by: (i) selective removal of several components from amniotic fluid and serum; (ii) selective addition of different components present in amniotic fluid and serum, including alpha-fetoprotein, to be radioimmunoassay; (iii) correlation between the inhibitory effect of both amniotic fluid and serum and between the amounts of alpha-fetoprotein they contain; (iv) blocking of the alpha-fetoprotein in vitro suggests a similar effect in vivo in pregnant women with myasthenia gravis. This effect may explain in part the variability in the development of neonatal myasthenia gravis in the babies, due to transplacental transfer of maternal anti-AcChoR antibody, only after delivery and only in the minority of the cases. It also may explain the appearnace of remissions in females with myasthenia gravis during the second and third trimesters of pregnancy. Similar phenomena observed during pregnancy in other autoimmune and immunopathogenic diseases also might be attributed to activity of alpha-fetoprotein. PMID:6158053

  18. Differential Diagnosis of Hallucinations in a Patient with Myasthenia Gravis

    PubMed Central

    Hizem, Yosr; Ben Djebara, Mouna; Kacem, Imen; Gargouri, Amina; Gouider, Riadh

    2013-01-01

    We present the case of a 63-year-old woman with comorbidity of myasthenia gravis and psychosis. Different diagnostic hypotheses based on a review of the literature are discussed. A protracted history of physical spousal abuse, patient symptoms, and results of different investigations allowed us to conclude that the patient had a form of posttraumatic stress disorder with secondary psychotic features. Psychosis due to myasthenia gravis is rarely seen, and it remains unclear what is the pathophysiology, if any, for such an association. The present case highlights the difficulties the physician faces in disentangling psychosis as a potential manifestation of myasthenia gravis itself versus being caused by a medical side effect of treatment, or psychosis due to a distinct co-occurring neurologic or psychiatric condition. PMID:24307978

  19. [Course and treatment of myasthenia gravis during pregnancy].

    PubMed

    Klehmet, J; Dudenhausen, J; Meisel, A

    2010-08-01

    Pregnancy and family planning issues are frequent concerns in the medical care of patients with myasthenia gravis since disease onset often coincides with the life period which is decisive in this respect. Although pregnancy, delivery and breastfeeding represent special circumstances in these patients, they are not associated with higher risks of complications compared to normal pregnancy, delivery and postpartum period. Frequently asked questions regard the course of pregnancy as well as the impact of the disease and particularly medical treatment on pregnancy and the foetus or neonate. Great significance is attached to the mode of delivery since it is still widely accepted that patients with myasthenia gravis have to deliver per elective caesarean section. This paper gives an overview and provides a basis for the medical care and individual counselling of patients with myasthenia gravis who want to start a family or are already pregnant. PMID:20411231

  20. Congenital myasthenic syndrome due to mutation in CHRNE gene with clinical worsening and thymic hyperplasia attributed to association with autoimmune-myasthenia gravis.

    PubMed

    Santos, Ernestina; Moreira, Isabel; Coutinho, Ester; Gonçalves, Guilherme; Lopes, Carlos; Lopes Lima, José; Leite, M Isabel

    2015-12-01

    We report a patient with congenital myasthenic syndrome (CMS) due to mutation in CHRNE with symptoms since the age of 4; mild to moderate fatigable weakness involved mainly ocular, bulbar and limb muscles; functional impact of the disease in their development and physical activity was modest. By the age of 34, the patient experienced gradual worsening of fatigue with dyspnoea and pronounced limb weakness, requiring significant increase of pyridostigmine. Further, a remarkable and sustained clinical improvement followed thymectomy with hyperplastic thymus. Despite of the absence of detectable antibodies to acetyl-choline receptor (AChR) (including clustered-AChR), muscle-specific kinase and low-density lipoprotein receptor-related protein-4 antibodies in the serum obtained nine years after thymectomy, the clinical, genetic and histological features are in keeping with the extremely rare association of two rare neuromuscular junction disorders - CMS and myasthenia gravis (MG). The inexistence of other conditions that could potentially associate with thymic hyperplasia also supports the diagnosis of MG. PMID:26363966

  1. T and B lymphocytes in myasthenia gravis.

    PubMed Central

    Itoyama, Y; Kawanami, S; Goto, I; Kuroiwa, Y

    1979-01-01

    Peripheral blood lymphocytes from seventeen non-thymectomized and nine thymectomized patients with myasthenia gravis (MG) and thirteen healthy controls were examined for the presence of surface markers characteristic of T and B lymphocytes by rosette formation with sheep red blood cells (SRBC). T cells were identified by their capacity to spontaneously form rosettes with SRBCs. The percentage of B lymphocytes was determined by the erythrocyte antibody complement (EAC) rosette-forming test. The EAC complex was prepared with either whole rabbit anti-SRBC serum or with the IgM fraction of rabbit anti-SRBC serum. The two kind of erythrocyte complement rosette-forming cells (EAC-RFC) are designated erythrocyte-haemolysin-complement RFC (EA(H)C-RFC), and erythrocyte-IgM-complement RFC (EA(M)C-RFC). The percentage of total lymphocytes and T cells was not altered in MG patients. The percentage of 'active' T cells, which have been considered to be more actively involved in cellular immunity, was also similar in MG patients and controls. A significant increase in EA(H)C-RFC occurred in both thymectomized and non-thymectomized MG patients, while in B cells detected by EA(M)C-RFC no alterations were found. The increase in EA(H)C-RFC in lymphocytes from MG patients may be due to an increase in the 19S antibody-forming B lymphocytes or to an increase in T cells which have Fc receptors on their surface. PMID:315844

  2. [Determination of prognostic factors in surgical treatment of myasthenia gravis].

    PubMed

    Schnorrer, M; Hraska, V; Spalek, P; Cársky, S

    1999-05-01

    The authors evaluated, using statistical analysis, the importance of prognostic factors in patients subjected to thymectomy on account of myasthenia gravis. The results revealed a better prognosis of the disease, if the history was less than 6 months, preoperative treatment less than 1.5 years, a histological finding of thymus hyperplasia, second clinical stage according to Ossermann and the patients age below 30 years. From the statistical analysis ensues that the prognosis of myasthenia gravis is more favourable when the case-history is shorter as a result of rapid diagnosis and when preoperative treatment is reduced to a minimum. PMID:10510623

  3. Myasthenia Gravis Presentation After a Cervical Laminectomy With Fusion.

    PubMed

    Deters, Darlene; Fowler, Stephanie L; Orozco, Raymundo; Smith, Patrick R; Spurlock, Shelby; Blackmon, Darlene; Thomas, Samantha

    2016-01-01

    Myasthenia gravis is a chronic neuromuscular disorder that causes skeletal muscle weakness. Typically, myasthenia gravis affects the ocular, bulbar, neck, proximal limbs, and respiratory muscles. Although the presentation is typically observed with complaints of vision and bulbar symptoms such as diplopia, dystonia, and dysphagia, this article presents a case study of an elderly man with a history of increasing upper extremity weakness with complaints of worsening hand dexterity and intermittent episodes of expressive aphasia. After cervical laminectomy with fusion, this gentleman was admitted to the medical intensive care unit, in a complete myasthenic crisis. PMID:27258955

  4. Paraneoplastic pemphigus and myasthenia gravis, associated with inflammatory pseudotumor-like follicular dendritic cell sarcoma: response to rituximab.

    PubMed

    Wang, Lifang; Deng, Hui; Mao, Mei

    2016-08-01

    Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease associated with neoplasms. The disease is most commonly of lymphoproliferative origin and presents high mortality. We describe a patient with PNP and myasthenia gravis associated with inflammatory pseudotumor-like follicular dendritic cell sarcoma, as well as the response to rituximab. PMID:27525088

  5. Determinants of quality of life in Brazilian patients with myasthenia gravis

    PubMed Central

    Mourão, Aline Mansueto; Gomez, Rodrigo Santiago; Barbosa, Luiz Sergio Mageste; da Silva Freitas, Denise; Comini-Frota, Elizabeth Regina; Kummer, Arthur; Lemos, Stella Maris Aguiar; Teixeira, Antonio Lucio

    2016-01-01

    OBJECTIVES: The aims of the current study were 1) to evaluate the reliability and validity of the Brazilian version of the 15-item Myasthenia Gravis Quality of Life Scale and 2) to investigate the quality of life of Brazilian patients with myasthenia gravis and its determinants. METHODS: This cross-sectional study included 69 patients with myasthenia gravis who underwent neurological evaluation and completed questionnaires regarding quality of life (the 36-item Short Form of the Medical Outcomes Study and the 15-item Myasthenia Gravis Quality of Life Scale), anxiety and depressive symptoms. RESULTS: The Brazilian version of the 15-item Myasthenia Gravis Quality of Life Scale showed high internal consistency and good concurrent validity with the 36-item Short Form of the Medical Outcomes Study and its subscales. Determinants of quality of life in Brazilian patients with myasthenia gravis included the current status of myasthenia gravis as assessed by the Myasthenia Gravis Composite, the current prednisone dose and the levels of anxiety and depression. CONCLUSION: The Brazilian version of the 15-item Myasthenia Gravis Quality of Life Scale is a valid instrument. Symptom severity, prednisone dosage and anxiety and depression levels impact the quality of life of patients with myasthenia gravis. PMID:27464292

  6. Myasthenia gravis and congenital myasthenic syndromes in dogs and cats: A history and mini-review.

    PubMed

    Shelton, G Diane

    2016-06-01

    Myasthenia gravis (MG) is a disorder of neuromuscular transmission in which muscle weakness results from an autoantibody mediated depletion of acetylcholine receptors (AChRs) at the neuromuscular junction. Myasthenia gravis occurs spontaneously in dogs and cats, and as in human MG, an autoimmune response against nicotinic AChRs has been demonstrated and autoantibodies against AChRs implicated in the pathogenesis. While both species are affected with MG, there are distinct differences in clinical presentations and frequency of spontaneous remission. Congenital myasthenic syndromes (CMSs) are hereditary disorders of neuromuscular transmission resulting in structural or functional defects of the neuromuscular junction. The clinical presentation and pathogenesis of a CMS in Jack Russell terriers was first described in the 1970's and 1980s and has since been reported in a few other breeds. Mutations have been reported in CHRNE, COLQ and CHAT in canine CMS. A form of COLQ deficient CMS has recently been reported in cats. PMID:27080328

  7. Muscle-Specific Receptor Tyrosine Kinase (MuSK) Myasthenia Gravis.

    PubMed

    Hurst, Rebecca L; Gooch, Clifton L

    2016-07-01

    Autoimmune myasthenia gravis (MG) is the prototypic, antibody-mediated neuromuscular disease and is characterized by a decrease in the number of functional acetylcholine receptors (AChR) within the muscle end plate zone of the neuromuscular junction (NMJ). Although the pathophysiology of AChR-mediated myasthenia gravis has been extensively studied over the last 40 years since its original description by Patrick and Lindstrom (Science 180:871-872, 1973), less is known about the much more recently described muscle-specific kinase (MuSK) antibody-mediated MG. MuSK-MG has features clinically distinct from Ach-R MG, as well as a different pattern of response to treatment and a unique immunopathogenesis. PMID:27170368

  8. Autoantibodies to Agrin in Myasthenia Gravis Patients

    PubMed Central

    Bealmear, Beverly; Ragheb, Samia; Xiong, Wen-Cheng; Lewis, Richard A.; Lisak, Robert P.; Mei, Lin

    2014-01-01

    To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. Two of the four triple negative MG patients (i.e., no detectable AChR, MuSK or LRP4 antibodies, AChR-/MuSK-/LRP4-) had antibodies against agrin. In addition, agrin antibodies were detected in 5 out of 83 AChR+/MuSK-/LRP4- patients but were not found in the 6 patients with MuSK antibodies (AChR-/MuSK+/LRP4-). Sera from MG patients with agrin antibodies were able to recognize recombinant agrin in conditioned media and in transfected HEK293 cells. These sera also inhibited the agrin-induced MuSK phosphorylation and AChR clustering in muscle cells. Together, these observations indicate that agrin is another autoantigen in patients with MG and agrin autoantibodies may be pathogenic through inhibition of agrin/LRP4/MuSK signaling at the NMJ. PMID:24632822

  9. Autoantibodies to agrin in myasthenia gravis patients.

    PubMed

    Zhang, Bin; Shen, Chengyong; Bealmear, Beverly; Ragheb, Samia; Xiong, Wen-Cheng; Lewis, Richard A; Lisak, Robert P; Mei, Lin

    2014-01-01

    To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. Two of the four triple negative MG patients (i.e., no detectable AChR, MuSK or LRP4 antibodies, AChR-/MuSK-/LRP4-) had antibodies against agrin. In addition, agrin antibodies were detected in 5 out of 83 AChR+/MuSK-/LRP4- patients but were not found in the 6 patients with MuSK antibodies (AChR-/MuSK+/LRP4-). Sera from MG patients with agrin antibodies were able to recognize recombinant agrin in conditioned media and in transfected HEK293 cells. These sera also inhibited the agrin-induced MuSK phosphorylation and AChR clustering in muscle cells. Together, these observations indicate that agrin is another autoantigen in patients with MG and agrin autoantibodies may be pathogenic through inhibition of agrin/LRP4/MuSK signaling at the NMJ. PMID:24632822

  10. Ocular myasthenia gravis after D-penicillamine administration.

    PubMed Central

    Katz, L J; Lesser, R L; Merikangas, J R; Silverman, J P

    1989-01-01

    A 68-year-old black woman who was put on D-penicillamine therapy (250-500 mg per day, total dose 15 g) for rheumatoid arthritis developed ocular myasthenia gravis. Two weeks after she discontinued D-penicillamine her signs and symptoms cleared with no other treatment. Review of previous cases and possible immunological mechanisms are discussed. PMID:2692700

  11. The effect of cholinesterase inhibitors of SFEMG in myasthenia gravis.

    PubMed

    Massey, J M; Sanders, D B; Howard, J F

    1989-02-01

    We report four patients with myasthenia gravis (MG) in whom single-fiber electromyography (SFEMG) jitter measurements were normal in some muslces while they were taking pyridostigmine and became abnormal 2-14 days after the medication was discontinued. When the abnormality of neuromuscular transmission in MG is mild, cholinesterase inhibitors may mask the findings of increased jitter on SFEMG. PMID:2540433

  12. Treatment of myasthenia gravis with high-dose intravenous immunoglobulin.

    PubMed

    Cosi, V; Lombardi, M; Piccolo, G; Erbetta, A

    1991-08-01

    We treated 37 patients affected by autoimmune generalized myasthenia gravis (MG) with high-dose intravenous gammaglobulin (HDIVIg), 400 mg/kg per day on 5 consecutive days. A one-degree improvement of Oosterhuis global clinical classification of myasthenic severity (OGCCMS), the disappearance of bulbar involvement or both were recorded 12 days after the beginning of the treatment in 70.3% of the patients and persisted up to 60 days in 58.7%. A two-degree improvement of OGCCMS was recorded in 54.1% of the patients and it was maintained up to 60 days in 37.8%. The percentage of improvement did not significantly differ between patients entering the treatment in a long-standing, drug-refractory stationary phase of the illness (n = 26) and patients who received HDIVIg in an acute phase of MG (n = 11). None of the patients experienced side effects. Our data indicates that HDIVIg is an interesting, virtually riskless therapeutic choice for MG patients, and allows the planning of a controlled trial versus plasma-exchange. PMID:1950455

  13. Myasthenia gravis - autoantibody characteristics and their implications for therapy.

    PubMed

    Gilhus, Nils Erik; Skeie, Geir Olve; Romi, Fredrik; Lazaridis, Konstantinos; Zisimopoulou, Paraskevi; Tzartos, Socrates

    2016-05-01

    Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies that target the neuromuscular junction, leading to muscle weakness and fatigability. Currently available treatments for the disease include symptomatic pharmacological treatment, immunomodulatory drugs, plasma exchange, thymectomy and supportive therapies. Different autoantibody patterns and clinical manifestations characterize different subgroups of the disease: early-onset MG, late-onset MG, thymoma MG, muscle-specific kinase MG, low-density lipoprotein receptor-related protein 4 MG, seronegative MG, and ocular MG. These subtypes differ in terms of clinical characteristics, disease pathogenesis, prognosis and response to therapies. Patients would, therefore, benefit from treatment that is tailored to their disease subgroup, as well as other possible disease biomarkers, such as antibodies against cytoplasmic muscle proteins. Here, we discuss the different MG subtypes, the sensitivity and specificity of the various antibodies involved in MG for distinguishing between these subtypes, and the value of antibody assays in guiding optimal therapy. An understanding of these elements should be useful in determining how to adapt existing therapies to the requirements of each patient. PMID:27103470

  14. Subcutaneous Immunoglobulin Therapy in the Chronic Management of Myasthenia Gravis: A Retrospective Cohort Study

    PubMed Central

    Bourque, P. R.; Pringle, C. E.; Cameron, W.; Cowan, J.; Chardon, J. Warman

    2016-01-01

    Background Immunoglobulin therapy has become a major treatment option in several autoimmune neuromuscular disorders. For patients with Myasthenia Gravis (MG), intravenous immunoglobulin (IVIg) has been used for both crisis and chronic management. Subcutaneous Immunoglobulins (SCIg), which offer the advantage of home administration, may be a practical and effective option in chronic management of MG. We analyzed clinical outcomes and patient satisfaction in nine cases of chronic disabling MG who were either transitioned to, or started de novo on SCIg. Methods and Findings This was a retrospective cohort study for the period of 2015–2016, with a mean follow-up period of 6.8 months after initiation of SCIg. All patients with MG treated with SCIg at the Ottawa Hospital, a large Canadian tertiary hospital with subspecialty expertise in neuromuscular disorders were included, regardless of MG severity, clinical subtype and antibody status. The primary outcome was MG disease activity after SCIg initiation. This outcome was measured by 1) the Myasthenia Gravis Foundation of America (MGFA) clinical classification, and 2) subjective scales of disease activity including the Myasthenia Gravis activities of daily living profile (MG-ADL), Myasthenia Gravis Quality-of-life (MG-QOL 15), Visual Analog (VA) satisfaction scale. We also assessed any requirement for emergency department visits or hospitalizations. Safety outcomes included any SCIg related complication. All patients were stable or improved for MGFA class after SCIg initiation. Statistically significant improvements were documented in the MG-ADL, MG-QOL and VAS scales. There were no exacerbations after switching therapy and no severe SCIg related complications. Conclusions SCIg may be a beneficial therapy in the chronic management of MG, with favorable clinical outcome and patient satisfaction results. PMID:27490101

  15. The mechanism of acetylcholine receptor in binding MuSK in myasthenia gravis and the role of HSP90 molecular chaperone

    PubMed Central

    Chen, Rongbo; Chen, Siqia; Liao, Juan; Chen, Xiaopu; Xu, Xiaoling

    2016-01-01

    As an autoimmune disease, myasthenia gravis is caused by the dysfunction of neural transmission. Acetylcholine is known to exert its function after entering into synaptic cleft through binding onto postsynaptic membrane. The role of acetylcholine in binding MuSK in myasthenia gravis, however, remains unknown. A total of 38 myasthenia gravis patients and 27 healthy controls were included in this study for the detection of the expression of MuSK using immunofluorescent method. Expression of both MuSK and interleukin-6 (IL-6) were measured by Western blot, followed by the correlation analysis between heat shock protein 90 (HSP90) and IL-6 which were measured by enzyme-linked immunosorbent assay (ELISA). In myasthenia gravis patients, MuSK was co-localized with acetylcholine at the postsynaptic membrane. Such accumulation of MuSK, however, did not occur in normal people. Meanwhile we also observed elevated expression of IL-6 in myasthenia gravis patients (p<0.05). ELISA assay showed higher expression of HSP90 in patients. Further signaling pathway screening revealed the activation of IL-6-mediated pathways including STAT3 and SPH2. In conclusion, MuSK was co-localized with acetylcholine in myasthenia gravis patients, with elevated expression. HSP90 in disease people can activate IL-6 mediated signaling pathways. PMID:27186300

  16. Future perspectives in target-specific immunotherapies of myasthenia gravis.

    PubMed

    Dalakas, Marinos C

    2015-11-01

    Myasthenia gravis (MG) is an autoimmune disease caused by complement-fixing antibodies against acetylcholine receptors (AChR); antigen-specific CD4+ T cells, regulatory T cells (Tregs) and T helper (Th) 17+ cells are essential in antibody production. Target-specific therapeutic interventions should therefore be directed against antibodies, B cells, complement and molecules associated with T cell signaling. Even though the progress in the immunopathogenesis of the disease probably exceeds any other autoimmune disorder, MG is still treated with traditional drugs or procedures that exert a non-antigen specific immunosuppression or immunomodulation. Novel biological agents currently on the market, directed against the following molecular pathways, are relevant and specific therapeutic targets that can be tested in MG: (a) T cell intracellular signaling molecules, such as anti-CD52, anti-interleukin (IL) 2 receptors, anti- costimulatory molecules, and anti-Janus tyrosine kinases (JAK1, JAK3) that block the intracellular cascade associated with T-cell activation; (b) B cells and their trophic factors, directed against key B-cell molecules; (c) complement C3 or C5, intercepting the destructive effect of complement-fixing antibodies; (d) cytokines and cytokine receptors, such as those targeting IL-6 which promotes antibody production and IL-17, or the p40 subunit of IL-12/1L-23 that affect regulatory T cells; and (e) T and B cell transmigration molecules associated with lymphocyte egress from the lymphoid organs. All drugs against these molecular pathways require testing in controlled trials, although some have already been tried in small case series. Construction of recombinant AChR antibodies that block binding of the pathogenic antibodies, thereby eliminating complement and antibody-depended-cell-mediated cytotoxicity, are additional novel molecular tools that require exploration in experimental MG. PMID:26600875

  17. Future perspectives in target-specific immunotherapies of myasthenia gravis

    PubMed Central

    Dalakas, Marinos C.

    2015-01-01

    Myasthenia gravis (MG) is an autoimmune disease caused by complement-fixing antibodies against acetylcholine receptors (AChR); antigen-specific CD4+ T cells, regulatory T cells (Tregs) and T helper (Th) 17+ cells are essential in antibody production. Target-specific therapeutic interventions should therefore be directed against antibodies, B cells, complement and molecules associated with T cell signaling. Even though the progress in the immunopathogenesis of the disease probably exceeds any other autoimmune disorder, MG is still treated with traditional drugs or procedures that exert a non-antigen specific immunosuppression or immunomodulation. Novel biological agents currently on the market, directed against the following molecular pathways, are relevant and specific therapeutic targets that can be tested in MG: (a) T cell intracellular signaling molecules, such as anti-CD52, anti-interleukin (IL) 2 receptors, anti- costimulatory molecules, and anti-Janus tyrosine kinases (JAK1, JAK3) that block the intracellular cascade associated with T-cell activation; (b) B cells and their trophic factors, directed against key B-cell molecules; (c) complement C3 or C5, intercepting the destructive effect of complement-fixing antibodies; (d) cytokines and cytokine receptors, such as those targeting IL-6 which promotes antibody production and IL-17, or the p40 subunit of IL-12/1L-23 that affect regulatory T cells; and (e) T and B cell transmigration molecules associated with lymphocyte egress from the lymphoid organs. All drugs against these molecular pathways require testing in controlled trials, although some have already been tried in small case series. Construction of recombinant AChR antibodies that block binding of the pathogenic antibodies, thereby eliminating complement and antibody-depended-cell-mediated cytotoxicity, are additional novel molecular tools that require exploration in experimental MG. PMID:26600875

  18. Multidisciplinary treatment for prepubertal juvenile myasthenia gravis with crisis.

    PubMed

    Hirata, Yusuke; Inoue, Masayoshi; Nabatame, Shin; Okumura, Meinoshin; Ozono, Keiichi

    2016-08-01

    The management of juvenile myasthenia gravis (MG) remains controversial. We report herein the case of a 12-year-old girl with prepubertal juvenile MG with respiratory crisis who underwent thymectomy following methylprednisolone pulse therapy. The patient initially developed progressively worsening fatigability, eyelid ptosis, and diplopia, followed by worsening generalized weakness, dysphagia, and dyspnea. Even after i.v. immunoglobulin, the patient presented with rapid onset of severe dyspnea requiring respiratory support with mechanical ventilation and was graded as Myasthenia Gravis Foundation of America class V. After a course of i.v. methylprednisolone pulse therapy, successful control of respiratory crisis was achieved, and trans-sternal thymectomy was performed. Partial remission was achieved postoperatively with oral pyridostigmine without immunosuppressive agents such as steroids or calcineurin inhibitors for 18 months after thymectomy. Early thymectomy following induction methylprednisolone pulse therapy might be a treatment option for prepubertal juvenile MG with severe respiratory crisis. PMID:27324449

  19. Myasthenia gravis on the Dutch antilles: an epidemiological study.

    PubMed

    Holtsema, H; Mourik, J; Rico, R E; Falconi, J R; Kuks, J B; Oosterhuis, H J

    2000-12-01

    We carried out an epidemiological study on the prevalence and annual incidence of myasthenia gravis on tropical islands Curaçao and Aruba in the period 1980-1995. Twenty-one patients (seven men and 14 women) were identified. The point prevalence increased from 29 per million in 1980 to about 70 per million in 1990-1995; the annual incidence over the total period was 4.7 per million. The female:male ratio was 2:1; purely ocular cases (2/21) comprised 9.5% and thymomas (4/21), 19%. These data are in accordance with most other epidemiological studies in non-tropical areas. No other studies on myasthenia gravis in tropical areas have been reported. PMID:11154803

  20. Thymic carcinoma in myasthenia gravis developing years after thymectomy.

    PubMed

    Katzberg, Hans D; Miller, Robert G; Katz, Jonathan

    2009-07-01

    We report two patients with myasthenia gravis (MG) who underwent thymectomy but developed thymic carcinoma years after the initial surgery. In one patient, the initial thymic pathology was normal, whereas the other had an encapsulated benign thymoma that was found only on pathological assessment. These cases demonstrate that MG may occur as part of a "new" paraneoplastic syndrome even after thymectomy. The late appearance of metastatic thymoma raises questions about monitoring for these patients. PMID:19533649

  1. MuSK-antibody positive myasthenia gravis: questions from the clinic.

    PubMed

    Sanders, Donald B; Juel, Vern C

    2008-09-15

    Clinical vignettes are presented of five patients with MuSK-antibody positive myasthenia gravis, each of which demonstrates a diagnostic or therapeutic issue that is unique to or characteristic of this condition. Consideration of these issues leads to questions, many of which are unanswered at this time, about the immunopathology and management of this subset of myasthenia gravis. PMID:18684517

  2. [Surgical treatment of myasthenia gravis in children].

    PubMed

    Iudin, Ia B; Kogan, O G; Prokopenko, Iu D; Klepikov, I I; Vusik, G V; Fedorov, K K; Ivanov, V V; Diupin, V A; Merzeniuk, O S

    1989-11-01

    The article deals with the treatment of myasthenia in 33 children whose ages ranged from 3 to 15 years. Myasthenia of moderate severity was diagnosed in 14, severe in 15, and extremely severe in 2 children. To make a precise diagnosis, loading, neostigmine methylsulfate, cold, and D-tubocurarine tests were conducted. Thymectomy was performed in 32 patients. The operation was carried out through a T-shaped sternotomy approach. Thymogenic myasthenia was verified in 31 patients and thymomogenic only in one patient. There were no fatal outcomes. The late-term results were studied in 12 patients in follow-up periods of 3 to 6 years. Adaptational activity of the patients, anticholinesterase agents and the results of stimulant electric myography served as the criterion in appraising the late-term results. Modern diagnostic methods and surgical intervention ensure a favourable result in 75% of patients. PMID:2615272

  3. Tacrolimus for myasthenia gravis: a clinical study of 212 patients.

    PubMed

    Ponseti, José M; Gamez, Josep; Azem, Jamal; López-Cano, Manuel; Vilallonga, Ramón; Armengol, Manuel

    2008-01-01

    Tacrolimus is a macrolide T cell immunomodulator that is used in myasthenia gravis (MG) patients to affect muscle contraction (ryanodine receptor by modulating intracellular calcium-release channels and increasing muscular strength), glucocorticoid receptors (increasing intracellular concentration of steroids and blocking the steroid export mechanism), and an increase in T cell apoptosis. In this study, we report the results of low-dose tacrolimus (0.1 mg/kg/day) treatment in 212 MG patients. There were 110 thymectomized, cyclosporine- and prednisone-dependent patients; 68 thymectomized patients who started tacrolimus early postoperatively (24 h after operation); and 34 patients over 60 years old with nonthymomatous generalized MG or in whom thymectomy was contraindicated. The mean follow-up time was 49.3 +/- 18.1 months. Muscular strength showed an increase of 23% after 1 month of treatment and 29% at the end of the study. The acetylcholine receptor antibodies decreased significantly from a mean of 33.5 nmol/L at base line to 7.8 nmol/L at the final visit. In the thymectomy group with combined prednisone and tacrolimus stratified by histology of the thymus, the mean probability to attain complete stable remission at 5 years was 80.8% in patients with hyperplasia, 48.1% in thymic involution, and 9.3% in patients with thymoma. In 4.9% of patients, tacrolimus was withdrawn because of major adverse effects. Our results suggest that a low dose of tacrolimus is effective for MG and could be included to the armamentarium for this autoimmune disease. The present results should be interpreted considering the limitations of a retrospective clinical study. Confirmation of these results in randomized studies is desirable. PMID:18096852

  4. 317 Myasthenia Gravis and Asthma, Relationship between Two Different Disorders of the Immune System

    PubMed Central

    Velasco-Medina, Andrea Aida; Barreto-Sosa, Adriana; Gonzalez-Carsolio, Aida; Burbano-Ceron, Andres-Leonardo; Velázquez-Sámano, Guillermo

    2012-01-01

    Background Myasthenia gravis is an autoimmune disease caused by absence of neuromuscular transmission due to antibodies directed against the nicotinic AChR located at the neuromuscular junction. The main symptoms include muscle weakness in the affected muscles, which is worse after its use. Diagnosis is made upon clinical manifestations and finding of IgG. Only 80 to 90% of patients with generalized disease are positive to these antibodies, and 30 to 50% with ophthalmologic manifestations. Other immunological alteration found in these patients is an overexpression of the low affinity IgE receptor (CD23). Asthma is characterized by shortness of breath, cough, wheezing and chest tightness caused by inflammation and a reversible contraction of bronchial smooth muscle. Immunologically is associated with a Th2 cytokine profile, mainly Il-4, Il-5, Il-13 and an increased IgE. Methods Allergic and autoimmune diseases represent an altered response of the immune system. Here we discuss the case of a patient who presented with an allergic disease at first then years later developed an autoimmune disease. Results Our patient had been diagnosed with persistent allergic rhinitis and asthma since 1992. He had been treated with inhaled corticosteroids, bronchodilators, intranasal corticosteroids, antihistamines and specific immunotherapy with control of symptoms. In June 2010 he noticed diplopia, palpebral ptosis and muscle weakness in upper extremities diagnosed with Myastenia gravis and started treatment with piridostigmine with adequate control of muscular symptoms. No thymoma was identified. Conclusions It has been noted the possible relationship between allergic and autoimmune diseases since in both there is an alteration in the regulatory mechanisms of the immune system. In this patient, we found the association between asthma and 19 years later the development of myasthenia gravis. Some of the explanations for this kind of association is the expression of CD23 in myasthenia

  5. The role of muscle-specific tyrosine kinase (MuSK) and mystery of MuSK myasthenia gravis

    PubMed Central

    Koneczny, Inga; Cossins, Judith; Vincent, Angela

    2014-01-01

    MuSK myasthenia gravis is a rare, severe autoimmune disease of the neuromuscular junction, only identified in 2001, with unclear pathogenic mechanisms. In this review we describe the clinical aspects that distinguish MuSK MG from AChR MG, review what is known about the role of MuSK in the development and function of the neuromuscular junction, and discuss the data that address how the antibodies to MuSK lead to neuromuscular transmission failure. PMID:23458718

  6. Novel Complement Inhibitor Limits Severity of Experimentally Myasthenia Gravis

    PubMed Central

    Soltys, Jindrich; Kusner, Linda L.; Young, Andrew; Richmonds, Chelliah; Hatala, Denise; Gong, Bendi; Shanmugavel, Vaithesh; Kaminski, Henry J.

    2011-01-01

    Objective Complement mediated injury of the neuromuscular junction is considered a primary disease mechanism in human myasthenia gravis and animal models of experimentally acquired myasthenia gravis (EAMG). We utilized active and passive models of EAMG to investigate the efficacy of a novel C5 complement inhibitor rEV576, recombinantly produced protein derived from tick saliva, in moderating disease severity. Methods Standardized disease severity assessment, serum complement hemolytic activity, serum cytotoxicity, acetylcholine receptor (AChR) antibody concentration, IgG subclassification, and C9 deposition at the neuromuscular junction were used to assess the effect of complement inhibition on EAMG induced by administration of AChR antibody or immunization with purified AChR. Results Administration of rEV576 in passive transfer EAMG limited disease severity as evidenced by 100% survival rate and a low disease severity score. In active EAMG, rats with severe and mild EAMG were protected from worsening of disease and had limited weight loss. Serum complement activity (CH50) in severe and mild EAMG was reduced to undetectable levels during treatment, and C9 deposition at the neuromuscular junction was reduced. Treatment with rEV576 resulted in reduction of toxicity of serum from severe and mild EAMG rats. Levels of total AChR IgG, and IgG2a antibodies were similar, but unexpectedly, the concentration of complement fixing IgG1 antibodies was lower in a group of rEV576-treated animals, suggesting an effect of rEV576 on cellular immunity. Interpretation Inhibition of complement significantly reduced weakness in two models of EAMG. C5 inhibition could prove to be of significant therapeutic value in human myasthenia gravis. PMID:19194881

  7. Myasthenia gravis and thymic neoplasms: A brief review

    PubMed Central

    Kumar, Ritesh

    2015-01-01

    Thymoma is the most common mediastinal tumor. They have varied presentation ranging from asymptomatic incidental mediastinal masses to locally extensive tumor with compressive symptoms and distant metastases. They have frequent association with various paraneoplastic syndromes (PNS). The most common PNS associated with thymoma is myasthenia gravis (MG). Patients of thymoma with MG have a favourable outcome due to early disclosure of the disease. Histologically they are classified into five subtypes and Masaoka-Koga staging system is used for staging. Surgery, chemotherapy and radiotherapy play an important role along with anti-myasthenia drugs. This review would like to highlight the association of thymoma with MG and associated clinical and therapeutic issues. PMID:26677446

  8. Myasthenia gravis: determinants for independent ventilation after transsternal thymectomy.

    PubMed

    Younger, D S; Braun, N M; Jaretzki, A; Penn, A S; Lovelace, R E

    1984-03-01

    We evaluated the respiratory function of 32 patients with myasthenia gravis who had transsternal thymectomy. Preoperative clinical, pulmonary function, and respiratory muscle pressure data were submitted to stepwise logistic regression analysis to identify preoperative factors that correlated with duration of supported ventilation after surgery. Ten patients (31%) had postoperative supported ventilation for more than 3 days. The duration of ventilatory support correlated most closely with maximal static expiratory pressure (r = 0.714, p less than 0.001). Expiratory weakness, by reducing cough efficacy, seems to be the main determinant that predicts need for longer postoperative supported ventilation. PMID:6538272

  9. The value of computed tomography in myasthenia gravis

    SciTech Connect

    Brown, L.R.; Muhm, J.R.; Sheedy, P.F. II; Unni, K.K.; Bernatz, P.E.; Hermann, R.C. Jr.

    1983-01-01

    In a 5 year study, 19 patients with myasthenia gravis were studied by computed tomography (CT) and underwent thymectomy. CT was accurate in detecting the nine true thymic masses but could not differentiate thymomas from nonthymomatous masses, including thymic cysts. No thymoma was found in a patient under 25 years of age. In one case, the 18 sec scanner could not differentiate a large gland from a thymoma. In eight cases, glands with histologic thymic hyperplasia and histologically normal thymus appeared to be similar and could not be differentiated by CT.

  10. Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms.

    PubMed

    Phillips, William D; Vincent, Angela

    2016-01-01

    Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms. PMID:27408701

  11. Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms

    PubMed Central

    Phillips, William D.; Vincent, Angela

    2016-01-01

    Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms. PMID:27408701

  12. Myasthenia gravis mimicking stroke: a case series with sudden onset dysarthria.

    PubMed

    Tremolizzo, Lucio; Giopato, Federico; Piatti, Maria Luisa; Rigamonti, Andrea; Ferrarese, Carlo; Appollonio, Ildebrando

    2015-06-01

    Myasthenia gravis (MG) is an immune-mediated disorder characterized by fluctuating fatigue of skeletal muscles, often involving extrinsic ocular or bulbar districts. Myasthenia gravis in the elderly is an under-recognized condition, sometimes confused with cerebrovascular disease. Here we present a case series of myasthenia patients which onset was characterized by sudden dysarthria, clearly raising this diagnostic dilemma. In the workout of sudden onset isolated dysarthria, MG should be always considered. In fact, even if myasthenia is a rare condition, lacunar stroke only with this clinical presentation is also unusual, and significant risks may arise (e.g., unexpected myasthenic crisis). PMID:25648108

  13. International consensus guidance for management of myasthenia gravis

    PubMed Central

    Wolfe, Gil I.; Benatar, Michael; Evoli, Amelia; Gilhus, Nils E.; Illa, Isabel; Kuntz, Nancy; Massey, Janice M.; Melms, Arthur; Murai, Hiroyuki; Nicolle, Michael; Palace, Jacqueline; Richman, David P.; Verschuuren, Jan; Narayanaswami, Pushpa

    2016-01-01

    Objective: To develop formal consensus-based guidance for the management of myasthenia gravis (MG). Methods: In October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness methodology was used to develop consensus guidance statements. Definitions were developed for goals of treatment, minimal manifestations, remission, ocular MG, impending crisis, crisis, and refractory MG. An in-person panel meeting then determined 7 treatment topics to be addressed. Initial guidance statements were developed from literature summaries. Three rounds of anonymous e-mail votes were used to attain consensus on guidance statements modified on the basis of panel input. Results: Guidance statements were developed for symptomatic and immunosuppressive treatments, IV immunoglobulin and plasma exchange, management of impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG associated with antibodies to muscle-specific tyrosine kinase, and MG in pregnancy. Conclusion: This is an international formal consensus of MG experts intended to be a guide for clinicians caring for patients with MG worldwide. PMID:27358333

  14. Sleep disorders in patients with myasthenia gravis: a systematic review.

    PubMed

    Fernandes Oliveira, Ezequiel; Nacif, Sergio R; Alves Pereira, Nixon; Fonseca, Nina Teixeira; Urbano, Jéssica Julioti; Perez, Eduardo Araújo; Cavalcante, Valéria; Santos Oliveira, Claudia; Insalaco, Giuseppe; Oliveira, Acary Sousa Bulle; Oliveira, Luis Vicente Franco

    2015-06-01

    [Purpose] This systematic review evaluated the presence of sleep-disordered breathing in patients with myasthenia gravis and clarified the role of physiotherapy. [Subjects and Methods] We followed the PRISMA declaration criteria. The evaluation was performed in accordance with the STROBE statement for observational and cross-sectional studies and the CONSORT checklist for clinical trials. Searches were followed by hand on MEDLINE, EMBASE, SciELO, PubMed Central, and the Cochrane Central Register of Controlled Trials. [Results] Our searches yielded a total of 36 studies published between 1970 and 2014. The number of patients involved ranged from 9-490. Of the 36 studies, 19 articles were excluded because they did not meet the inclusion criteria. Therefore, 17 observational, cross-sectional, or clinical studies assessing the quality of sleep and prevalence of sleep disorders in patients with myasthenia gravis were eligible for our review. [Conclusion] Some studies of patients with MG show that patients with MG are associated with poor sleep quality, excessive daytime sleepiness, presence of restless syndrome, and a higher incidence of SDB, while other studies do not report such associations. Therefore, given the current inconclusive evidence and limited literature, further study of sleep disturbances in patients with MG is needed. PMID:26180370

  15. Sleep disorders in patients with myasthenia gravis: a systematic review

    PubMed Central

    Fernandes Oliveira, Ezequiel; Nacif, Sergio R.; Alves Pereira, Nixon; Fonseca, Nina Teixeira; Urbano, Jéssica Julioti; Perez, Eduardo Araújo; Cavalcante, Valéria; Santos Oliveira, Claudia; Insalaco, Giuseppe; Oliveira, Acary Sousa Bulle; Oliveira, Luis Vicente Franco

    2015-01-01

    [Purpose] This systematic review evaluated the presence of sleep-disordered breathing in patients with myasthenia gravis and clarified the role of physiotherapy. [Subjects and Methods] We followed the PRISMA declaration criteria. The evaluation was performed in accordance with the STROBE statement for observational and cross-sectional studies and the CONSORT checklist for clinical trials. Searches were followed by hand on MEDLINE, EMBASE, SciELO, PubMed Central, and the Cochrane Central Register of Controlled Trials. [Results] Our searches yielded a total of 36 studies published between 1970 and 2014. The number of patients involved ranged from 9–490. Of the 36 studies, 19 articles were excluded because they did not meet the inclusion criteria. Therefore, 17 observational, cross-sectional, or clinical studies assessing the quality of sleep and prevalence of sleep disorders in patients with myasthenia gravis were eligible for our review. [Conclusion] Some studies of patients with MG show that patients with MG are associated with poor sleep quality, excessive daytime sleepiness, presence of restless syndrome, and a higher incidence of SDB, while other studies do not report such associations. Therefore, given the current inconclusive evidence and limited literature, further study of sleep disturbances in patients with MG is needed. PMID:26180370

  16. Anti-MuSK myasthenia gravis with prolonged remission.

    PubMed

    Bouwyn, Jean Paul; Magnier, Patrick; Bédat-Millet, Anne-Laure; Ahtoy, Patrick; Maltête, David; Lefaucheur, Romain

    2016-07-01

    Myasthenia gravis (MG) with antibodies against muscle-specific tyrosine kinase (MuSK) is a rare disorder of neuromuscular transmission affecting preferentially bulbar, neck and respiratory muscles. We report the case of a 22-year-old man who presented with diplopia on lateral gaze to both sides, facial diplegia, nasal dysarthria and dysphagia. Repetitive nerve stimulation of the trapezius and orbicularis oculi muscles showed amplitude decrements of 19% and 41% respectively supporting the diagnosis of myasthenia gravis. MUsK antibodies were positive. Corticosteroids were introduced and then tapered and discontinued at 6 months after initiation. The patient remained in remission and asymptomatic for 4 years without ongoing treatment or prior treatment with rituximab after this first relapse of MuSK-MG. MuSK- MG is considered a hard-to-treat condition and patients generally remain dependent on immunosuppression or prior treatment with rituximab. Our observation highlights that patients with MuSK-MG can have a benign course and that continued immunosuppressive or immunomodulatory therapy may not always be required. PMID:27161384

  17. Myasthenia Gravis Development and Crisis Subsequent to Multiple Sclerosis

    PubMed Central

    Gharagozli, Kurosh; Shojaei, Maziar; Harandi, Ali Amini; Akbari, Nayyereh; Ilkhani, Manouchehr

    2011-01-01

    During the last decade, sporadic combination of multiple sclerosis (MS) and myasthenia gravis (MG) has been reported repeatedly. Although these are anecdotal, they are important enough to raise concerns about co-occurrence of MG and MS. Here, we present a case of an MS patient who developed an MG crisis. She had received interferon for relapsing remitting MS. Interestingly, she developed an MG crisis 4 years after the diagnosis of MS. MS and MG have relatively the same distribution for age, corresponding to the younger peak of the bimodal age distribution in MG. They also share some HLA typing characteristics. Furthermore, some evidences support the role of systemic immune dysregulation due to a genetic susceptibility that is common to these two diseases. The association may be underdiagnosed because of the possible overlap of symptoms especially bulbar manifestations in which either MG or MS can mimic each other, leading to underestimating incidence of the combination. The evidence warrants physicians, especially neurologists, to always consider the possibility of the other disease when encountering any patients either with MS or MG. Anecdotal and sporadic reports of combination of multiple sclerosis (MS) and myasthenia gravis (MG) have been raised concerns about co-occurrence of them. PMID:21629802

  18. Thymectomy Cures Diabetes Mellitus and Ameliorates Myasthenia Gravis in a Patient with Thymus Hyperplasia and Hyperthyroidism: Report of a Case.

    PubMed

    Feng, Shiyun; Zhang, Yao; Cui, Youbin; Chen, Yu

    2015-12-01

    Myasthenia gravis (MG) is a devastating autoimmune disease that involves the acetylcholine receptor (AchR) in the postsynaptic membrane of the neuromuscular junction. It is not uncommon for MG to accompany with other autoimmune diseases and complicate with multiple organ dysfunction. Here, we report on an 18-year-old female patient with a rare case of MG concomitant with thymus hyperplasia, diabetes mellitus, and hyperthyroidism. After full excision of the hyperplastic thymus gland, the patient's muscle weakness was greatly improved and her blood glucose level was restored to normal at the 6-month follow-up. PMID:26884666

  19. Ocular myasthenia gravis. A critical review of clinical and pathophysiological aspects.

    PubMed

    Sommer, N; Melms, A; Weller, M; Dichgans, J

    1993-01-01

    Myasthenia gravis (MG) is probably the best studied autoimmune disease caused by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction, subsequently leading to abnormal fatigability and weakness of skeletal muscle. Extraocular muscle weakness with droopy eyelids and double vision is present in about 90% of MG patients, being the initial complaint in about 50%. In approximately 20% of the patients the disease will always be confined to the extraocular muscles. The single most important diagnostic test is the detection of serum antibodies against AChR which is positive in 90% of patients with generalized MG, but only in 65% with purely ocular MG. Electromyographic studies and the Tensilon test are of diagnostic value in clear-cut cases, but may be equivocal in purely ocular myasthenia, especially the latter not rarely producing false-positive results. Treatment response to corticosteroids and anti-cholinesterase agents is satisfactory in many patients with ocular MG, however other immunosuppressive drugs may also be needed. Pathogenetically relevant steps of the underlying autoimmune process have been elucidated during the last few years; nevertheless a number of questions remain open, especially what starts off the autoimmune process, and why are eye muscles so frequently involved in MG? PMID:8156854

  20. Anesthetic Management of a Patient with Myasthenia Gravis for Meningioma Surgery - A Case Report.

    PubMed

    Srivastava, V K; Agrawal, S; Ahmed, M; Sharma, S

    2015-01-01

    Myasthenia gravis is a disease of great challenge to the anesthesiologist, because it affects the neuromuscular junction. Anesthetic management involves either muscle relaxant or non-muscle relaxant techniques. This case report documents the safe use of fentanyl, propofol and sevoflurane combination guided by bispectral index, without the use of muscle relaxants in a patient with myasthenia gravis who presented for meningioma surgery. PMID:26620756

  1. Unusual clinical behaviour of thymoma with recurrent myasthenia gravis.

    PubMed

    Keditsu, Keduovinuo K; Karimundackal, George; Jambhekar, Nirmala A; Pramesh, C S

    2012-06-01

    A 58-year old man with thymoma and myasthenia gravis (MG) had undergone thymectomy 8 years ago with histopathologically confirmed non-invasive WHO-type AB thymoma. After 5 years of complete remission, symptoms of MG resurfaced, and a recurrent anterior mediastinal mass was detected for which he received radiotherapy. He presented to us 3 years later with productive cough and exertional dyspnoea; the positron emission tomography-computed tomography scan revealed a metabolically active pulmonary nodule in the right lung as the only site of disease for which a right lower lobectomy was done. Microscopy established an intrapulmonary WHO-type B2 thymoma and the patient is currently asymptomatic on steroids, anticholinesterase and immunosuppressant therapy. We discuss the variable and unpredictable course of thymomas; the possibility of transformation into more aggressive types with each recurrence, association with recurrent MG post-thymectomy and presentation several years later with metastatic disease. PMID:22378319

  2. Myasthenia gravis and amyotrophic lateral sclerosis: A pathogenic overlap.

    PubMed

    Gotaas, Håvard Torvik; Skeie, Geir Olve; Gilhus, Nils Erik

    2016-06-01

    The aim was to examine potential joint disease mechanisms for myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS) through the examination of long-term patient cohorts for comorbidity. Recent studies support early involvement of the neuromuscular junction in ALS patients with subsequent degeneration of motor neurons. Medical records at Haukeland University Hospital from 1987 to 2012 were examined for International Classification of Diseases diagnostic codes for MG and ALS. Sera were re-tested for antibodies to acetylcholine receptor, titin, MuSK and GM1. We report one patient with both MG and ALS, and another 3 patients with suggestive evidence of both conditions. This is far more than expected from prevalence and incidence figures in this area if the disorders were unrelated. Our data suggest that immunological mechanisms in the neuromuscular junction are relevant in ALS pathogenesis. Attention should be given to possible therapeutic targets in the neuromuscular junction and muscle in ALS patients. PMID:27102003

  3. Elderly-onset familial myasthenia gravis in two siblings.

    PubMed

    Hirunagi, Tomoki; Tsujikawa, Koyo; Hasegawa, Yasuhiro; Mano, Kazuo; Katsuno, Masahisa

    2016-06-01

    Myasthenia gravis (MG) occasionally occurs in a family, but elderly-onset (≥65 years) familial MG has been rarely reported. We here report the case of two siblings with elderly-onset MG (mean onset age: 72.5 years) and present the human leukocyte antigen (HLA) profiles (HLA-A, -B, -DR) of their family. Both patients developed generalized MG with elevated serum acetylcholine receptor antibody titers at their seventies. Of six siblings, the two patients and one unaffected sibling shared the same HLA haplotypes. Our study indicates that elderly-onset MG can occur in a family and that familial occurrence of MG may be related to certain HLA alleles. PMID:27132121

  4. The search for new antigenic targets in myasthenia gravis.

    PubMed

    Cossins, Judith; Belaya, Katsiaryna; Zoltowska, Katarzyna; Koneczny, Inga; Maxwell, Susan; Jacobson, Leslie; Leite, Maria Isabel; Waters, Patrick; Vincent, Angela; Beeson, David

    2012-12-01

    Around 80% of myasthenia gravis patients have antibodies against the acetylcholine receptor, and 0-60% of the remaining patients have antibodies against the muscle-specific tyrosine kinase, MuSK. Another recently identified antigen is low-density lipoprotein receptor-related protein 4 (Lrp4). To improve the existing assays and widen the search for new antigenic targets, we have employed cell-based assays in which candidate target proteins are expressed on the cell surface of transfected cells and probed with patient sera. These assays, combined with use of myotube cultures to explore the effects of the antibodies, enable us to begin to identify new antigenic targets and test antibody pathogenicity in vitro. PMID:23278587

  5. Extracorporeal Immunoglobulin Elimination for the Treatment of Severe Myasthenia Gravis

    PubMed Central

    Blaha, M.; Pit'ha, J.; Blaha, V.; Lanska, M.; Maly, J.; Filip, S.; Langrova, H.

    2010-01-01

    Myasthenia gravis (MG) is a neuromuscular disorder leading to fluctuating muscle weakness and fatigue. Rarely, long-term stabilization is not possible through the use of thymectomy or any known drug therapy. We present our experience with extracorporeal immunoglobulin (Ig) elimination by immunoadsorption (adsorbers with human Ig antibodies). Acetylcholine receptor antibodies (AChRAs) were measured during long-term monitoring (4.7 ± 2.9 years; range 1.1–8.0). A total of 474 samples (232 pairs) were analyzed, and a drop in AChRA levels was observed (P = .025). The clinical status of patients improved and stabilized. Roughly 6.8% of patients experienced clinically irrelevant side effects. The method of Ig elimination by extracorporeal immunoadsorption (IA) is a clinical application of the recent biotechnological advances. It offers an effective and safe therapy for severe MG even when the disease is resistant to standard therapy. PMID:20300435

  6. [Onset of myasthenia gravis in primary care. Presentation of a case].

    PubMed

    Álvarez-Cordovés, M M; Mirpuri-Mirpuri, P G; Pérez-Monje, A

    2013-10-01

    Myasthenia gravis is an autoimmune disorder of neuromuscular transmission involving the production of autoantibodies directed against skeletal muscle receptors, in most cases of acetylcholine. Clinically it is characterized by the appearance of muscle weakness after prolonged activity, which tends to recover after a period of rest, or administration of acetylcholinesterase inhibitors. It is a relatively rare disease, although the prevalence has increased by improved diagnosis and increased longevity of the population. The diagnosis can be based on evidence after it is suspected using pharmacological, immunological or electrophysiology tests. Treatment can be divided into: symptomatic, short term and long term. We report the case of a patient who complained of diplopia, this muscle weakness being the most common initial symptom of the disease. PMID:24095170

  7. Autoantibody profile and clinical characteristics in a cohort of Chinese adult myasthenia gravis patients.

    PubMed

    Hong, Yu; Li, Hai-Feng; Skeie, Geir Olve; Romi, Fredrik; Hao, Hong-Jun; Zhang, Xu; Gao, Xiang; Owe, Jone Furlund; Gilhus, Nils Erik

    2016-09-15

    Myasthenia gravis (MG) is an autoimmune disorder with heterogeneity. Antibodies against acetylcholine receptor (AChR), muscle-specific kinase (MuSK), titin and ryanodine receptor (RyR) were examined in 437 adult Chinese MG patients. The AChR, MuSK, titin and RyR antibodies were found in 82.2%, 2.3%, 28.4% and 23.8% of all patients. Autoantibody profiles vary among different MG subgroups. Thymoma MG patients had high frequencies of AChR (99.2%), titin (50.8%) and RyR antibodies (46.9%). The titin and RyR antibodies also showed high frequencies in late onset patients (54.4% and 33.3%, respectively). These two antibodies may indicate an underlying thymoma when combined. The patients with titin and RyR antibodies tend to have more severe disease and worse outcome, and may need more active immunosuppressive treatment. PMID:27609275

  8. Serum Metabolomic Response of Myasthenia Gravis Patients to Chronic Prednisone Treatment

    PubMed Central

    Sengupta, Manjistha; Cheema, Amrita; Kaminski, Henry J.; Kusner, Linda L.

    2014-01-01

    Prednisone is often used for the treatment of autoimmune and inflammatory diseases but they suffer from variable therapeutic responses and significant adverse effects. Serum biological markers that are modulated by chronic corticosteroid use have not been identified. Myasthenia gravis is an autoimmune neuromuscular disorder caused by antibodies directed against proteins present at the post-synaptic surface of neuromuscular junction resulting in weakness. The patients with myasthenia gravis are primarily treated with prednisone. We analyzed the metabolomic profile of serum collected from patients prior to and after 12 weeks of prednisone treatment during a clinical trial. Our aim was to identify metabolites that may be treatment responsive and be evaluated in future studies as potential biomarkers of efficacy or adverse effects. Ultra-performance liquid chromatography coupled with electro-spray quadrupole time of flight mass spectrometry was used to obtain comparative metabolomic and lipidomic profile. Untargeted metabolic profiling of serum showed a clear distinction between pre- and post- treatment groups. Chronic prednisone treatment caused upregulation of membrane associated glycerophospholipids: phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, 1, 2-diacyl-sn glycerol 3 phosphate and 1-Acyl-sn-glycero-3-phosphocholine. Arachidonic acid (AA) and AA derived pro-inflammatory eicosanoids such as 18-carboxy dinor leukotriene B4 and 15 hydroxyeicosatetraenoic acids were reduced. Perturbations in amino acid, carbohydrate, vitamin and lipid metabolism were observed. Chronic prednisone treatment caused increase in membrane associated glycerophospholipids, which may be associated with certain adverse effects. Decrease of AA and AA derived pro-inflammatory eicosanoids demonstrate that immunosuppression by corticosteroid is via suppression of pro-inflammatory pathways. The study identified metabolomic fingerprints that can now be validated as prednisone

  9. Clinical characteristics and therapeutic evaluation of childhood myasthenia gravis

    PubMed Central

    YANG, ZHI-XIAO; XU, KAI-LI; XIONG, HUI

    2015-01-01

    This study aimed to analyze the clinical characteristics, classification and treatment of childhood myasthenia gravis (MG) and address the prognosis through follow-up. The clinical data of 135 children with MG were grouped according to clinical type and therapeutic drugs, retrospectively analyzed and prospectively monitored. Of the 135 MG patients, 85.2% had type I (ocular type), with only 4.2% progressing to systemic MG; 13.4% had type II (general type); and 1.5% had type III (fulminating type). Relapse occurred in 46.1% of the 102 patients that were followed up. The positive rate for the primary acetylcholine receptor antibody was 40.19%, without significant differences among clinical subtypes. The positive rate of the repetitive nerve stimulation frequency test by electromyography was 37.97%. Decreased expression of CD4+, CD8+, or CD3+ was present in 71% of the patients. Thymic hyperplasia was present in 5.93% of the patients, while 1.48% had thymoma. Steroid treatment was effective in the majority of the patients. Ocular type MG was common in this cohort of patients. The incidence and mortality of myasthenia crisis were low, the presence of concurrent thymoma was rare and only a limited number of children developed neurological sequelae. PMID:25780436

  10. Mechanism of nasal tolerance induced by a recombinant fragment of acetylcholine receptor for treatment of experimental myasthenia gravis.

    PubMed

    Im, S H; Barchan, D; Fuchs, S; Souroujon, M C

    2000-11-01

    Acetylcholine receptor (AChR) is the major autoantigen in myasthenia gravis (MG) and experimental autoimmune MG (EAMG). Here we analyze the mechanisms involved in suppression of ongoing EAMG in rats by nasal administration of a recombinant fragment from the human AChR alpha-subunit. We demonstrate that such a fragment, expressed without a fusion partner, confers nasal tolerance that can be adoptively transferred. Our observations suggest that the underlying mechanism of this nasal tolerance is active suppression involving a shift from a Th1 to a Th2/Th3-regulated AChR-specific response which may be mediated by down regulation of costimulatory factors. PMID:11063834

  11. Fusion protein of single-chain variable domain fragments for treatment of myasthenia gravis

    PubMed Central

    Li, Fangfang; Meng, Fanping; Jin, Quanxin; Sun, Changyuan; Li, Yingxin; Li, Honghua; Jin, Songzhu

    2014-01-01

    Single-chain variable domain fragment (scFv) 637 is an antigen-specific scFv of myasthenia gravis. In this study, scFv and human serum albumin genes were conjugated and the fusion protein was expressed in Pichia pastoris. The affinity of scFv-human serum albumin fusion protein to bind to acetylcholine receptor at the neuromuscular junction of human intercostal muscles was detected by immunofluorescence staining. The ability of the fusion protein to block myasthenia gravis patient sera binding to acetylcholine receptors and its stability in healthy serum were measured by competitive ELISA. The results showed that the inhibition rate was 2.0-77.4%, and the stability of fusion protein in static healthy sera was about 3 days. This approach suggests the scFv-human serum albumin is a potential candidate for specific immunosuppressive therapy of myasthenia gravis. PMID:25206900

  12. Seropositivity for West Nile Virus Antibodies in Patients Affected by Myasthenia Gravis

    PubMed Central

    Greco, Marilena; Cofano, Pietro; Lobreglio, Giambattista

    2016-01-01

    Background Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal muscles. Specific auto-antibodies against acetylcholine receptor (AChR) are present in the majority of MG patients, although the main cause behind its development still remains unclear. Recently MG development following West Nile virus (WNV) infection has been described in patients without any earlier evidence of MG. It is known that infectious agents trigger immune response and occasionally initiate autoimmune disease. WNV, the causative agent of both benign illness and neuroinvasive disease, has become endemic in many countries in all continents. Methods In the present study, 29 patients (15 males and 14 females, 19 - 78 years old) with confirmed diagnosis of MG and elevated levels of AChR autoantibodies were screened for the presence of serum anti-WNV antibodies and compared to a similar population affected by different autoimmune diseases. Indirect immunofluorescent antibody technique was used to evaluate the reaction of patients’ sera on cells infected by WNV. Results Positive fluorescent signals for anti-WNV IgG were obtained in 17% of MG patients, although no clinical manifestations related to WNV infection were reported. These results are in agreement with previous data and appear of great interest in the understanding of the pathogenic autoimmune mechanisms at the bases of MG development. Conclusion As already observed in other human autoimmune diseases, pathogen-triggered autoimmunity could be involved in MG by breaking immunological self-tolerance through possible mechanisms of molecular mimicry between virus proteins and AChR subunits. In predisposed individuals, WNV infection could also represent an additional risk factor to initiate MG. PMID:26858791

  13. Subcostal thoracoscopic extended thymectomy for patients with myasthenia gravis

    PubMed Central

    Tang, Yong; Ou, Zhu-An; Liao, Ming; Xuan, Yiwen; Su, Kai; Xu, En-Wu; Xiao, Haiping; Peng, Xiufan; Zhang, Zhuohua; Liu, Yan

    2016-01-01

    Background Extended thymectomy is indicated for patients with myasthenia gravis (MG) when drug-resistance or dependence is seen. We have employed a technique for subcostal thoracoscopic extended thymectomy (STET) on patients with MG. Methods Clinical data of 15 eligible patients who underwent STET in our department from February 2015 to November 2015 by the same surgical team were retrospectively analyzed. The operation time, blood loss, duration of postoperative hospital stay, thoracic drainage periods were concerned. Results All the surgeries were finished successfully without conversion to sternotomy. Mean operation time was 157.53±40.31 min (range, 73–275 min). Mean blood loss was 56.33±7.07 mL (range, 10–200 mL). Mean pleural drainage volume in the first 24 hours was 72.67±17.68 mL (range, 0–250 mL). Mean postoperative thoracic drainage periods were 1.20±0.71 days (range, 0–3 days). Mean duration of postoperative hospital stay was 6.13±0.71 days (range, 3–22 days). Conclusions This procedure showed satisfactory results for patients with MG. Moreover, the STET approach is more easily for surgeons to fully reveal the bilateral phrenic nerve and the upper thymic poles. We believe that STET is a satisfactory procedure for performing extended thymectomy in well selected patients. PMID:27076946

  14. Complications of radiologic contrast in patients with myasthenia gravis.

    PubMed

    Mehrizi, Mehyar; Pascuzzi, Robert M

    2014-09-01

    Use of older contrast agents during radiologic imaging in patients with myasthenia gravis (MG) has been associated with increased myasthenic symptoms and adverse drug reactions (ADRs). The effects of newer contrast agents have not been determined. A retrospective review of imaging safety in MG was conducted. Three hundred fifty-four imaging studies were analyzed. Procedures included 189 computed tomography (CT) images with and 106 without intravenous (IV) contrast and 42 magnetic resonance images (MRIs) with and 17 without contrast. In 108 patients for whom there was formal documentation of presence or absence of an immediate adverse response, only 1 who received CT IV contrast had an ADR (rate 0.93%). No ADRs or weakness were reported in patients who received MRI IV contrast. Our data suggest there is no significant immediate increased risk of myasthenic weakness with the use of modern radiologic contrast agents. The rate of ADRs in MG patients who receive CT IV contrast is now very low (0.93%). PMID:24677227

  15. Changes in inflammatory cytokine networks in myasthenia gravis.

    PubMed

    Uzawa, Akiyuki; Kanai, Tetsuya; Kawaguchi, Naoki; Oda, Fumiko; Himuro, Keiichi; Kuwabara, Satoshi

    2016-01-01

    Myasthenia gravis (MG) is an autoimmunological inflammatory disorder of the neuromuscular junction. Inflammation could be a key player for understanding the pathogenesis of MG. We measured the serum levels of 24 inflammatory cytokines in 43 patients with anti-acetylcholine receptor antibody-positive MG and 25 healthy controls. In patients with MG, serum levels of a proliferation-inducing ligand (APRIL), IL-19, IL-20, IL-28A and IL-35 were significantly increased as compared with controls (p < 0.05). Among them, IL-20, IL-28A and IL-35 were significantly decreased after treatment (p < 0.05). In clinical subtype analyses, APRIL and IL-20 were increased in patients with late-onset MG and IL-28A levels were increased in patients with thymoma-associated MG compared with healthy controls (p < 0.01). The results of the present study demonstrate both anti-inflammatory and inflammatory cytokines are upregulated in MG, reflecting the importance of cytokine-mediated inflammation and its regulation in MG pathophysiology. PMID:27172995

  16. HLA antigens in Japanese patients with myasthenia gravis.

    PubMed Central

    Matsuki, K; Juji, T; Tokunaga, K; Takamizawa, M; Maeda, H; Soda, M; Nomura, Y; Segawa, M

    1990-01-01

    HLA antigens in 104 Japanese patients and 41 families with myasthenia gravis (MG) were investigated. The frequencies of DR9 and DRw13 were significantly increased in the patients who developed MG before 3 yr of age. The DQw3 antigen was positive for all the patients that developed MG before 15 yr with only one exception. All the examined cases that developed MG before 3 yr (including this DQw3 negative patient) had the same DQA and DQB DNA restriction fragments. These HLA frequencies decreased as the age of onset increased, and no significant association was observed in adult-onset MG. No patients had B8, DR3, and DQw2. The relative risk was higher for the DR9/DRw13 heterozygotes (37.4) than for DR9 (16.4) or DRw13 (7.1) in the childhood-onset MG. Statistical analysis suggested that DR9 and DRw13 (or DQw1 and DQw3) act synergistically in the disease development. Family study revealed diverse DR9 haplotypes. The most frequent DRw13 haplotype was Bw44-BFF-C4A3B1-DRw13-DQw1, which may be evolutionarily related to the caucasian B8-DR3-DQw2 haplotype. These results showed that MG in early childhood in Japanese individuals is genetically different from that in adulthood and that in caucasians. Images PMID:1974553

  17. Changes in inflammatory cytokine networks in myasthenia gravis

    PubMed Central

    Uzawa, Akiyuki; Kanai, Tetsuya; Kawaguchi, Naoki; Oda, Fumiko; Himuro, Keiichi; Kuwabara, Satoshi

    2016-01-01

    Myasthenia gravis (MG) is an autoimmunological inflammatory disorder of the neuromuscular junction. Inflammation could be a key player for understanding the pathogenesis of MG. We measured the serum levels of 24 inflammatory cytokines in 43 patients with anti-acetylcholine receptor antibody-positive MG and 25 healthy controls. In patients with MG, serum levels of a proliferation-inducing ligand (APRIL), IL-19, IL-20, IL-28A and IL-35 were significantly increased as compared with controls (p < 0.05). Among them, IL-20, IL-28A and IL-35 were significantly decreased after treatment (p < 0.05). In clinical subtype analyses, APRIL and IL-20 were increased in patients with late-onset MG and IL-28A levels were increased in patients with thymoma-associated MG compared with healthy controls (p < 0.01). The results of the present study demonstrate both anti-inflammatory and inflammatory cytokines are upregulated in MG, reflecting the importance of cytokine-mediated inflammation and its regulation in MG pathophysiology. PMID:27172995

  18. Diagnosis of Tensilon-Negative Ocular Myasthenia Gravis By Daily Selfie.

    PubMed

    Guterman, Elan L; Botelho, James V; Horton, Jonathan C

    2016-09-01

    The initial symptoms of myasthenia gravis are usually ptosis and diplopia. The diagnosis is often confirmed by testing for anti-acetylcholine receptor antibodies or by observing the effects of intravenous edrophonium (Tensilon) injection. However, these standard tests may be negative in patients with isolated ocular findings. We present the case of an 83-year-old woman with negative serologic and Tensilon testing. She was asked to photograph herself daily. The resulting sequence of daily selfies captured striking fluctuations in her ocular alignment and ptosis. Daily selfies may be a useful strategy for confirming the clinical diagnosis of ocular myasthenia gravis. PMID:27529328

  19. Novel CXCL13 transgenic mouse: inflammation drives pathogenic effect of CXCL13 in experimental myasthenia gravis

    PubMed Central

    Weiss, Julia Miriam; Robinet, Marieke; Aricha, Revital; Cufi, Perrine; Villeret, Bérengère; Lantner, Frida; Shachar, Idit; Fuchs, Sara; Souroujon, Miriam C.

    2016-01-01

    Abnormal overexpression of CXCL13 is observed in many inflamed tissues and in particular in autoimmune diseases. Myasthenia gravis (MG) is a neuromuscular disease mainly mediated by anti-acetylcholine receptor autoantibodies. Thymic hyperplasia characterized by ectopic germinal centers (GCs) is a common feature in MG and is correlated with high levels of anti-AChR antibodies. We previously showed that the B-cell chemoattractant, CXCL13 is overexpressed by thymic epithelial cells in MG patients. We hypothesized that abnormal CXCL13 expression by the thymic epithelium triggered B-cell recruitment in MG. We therefore created a novel transgenic (Tg) mouse with a keratin 5 driven CXCL13 expression. The thymus of Tg mice overexpressed CXCL13 but did not trigger B-cell recruitment. However, in inflammatory conditions, induced by Poly(I:C), B cells strongly migrated to the thymus. Tg mice were also more susceptible to experimental autoimmune MG (EAMG) with stronger clinical signs, higher titers of anti-AChR antibodies, increased thymic B cells, and the development of germinal center-like structures. Consequently, this mouse model finally mimics the thymic pathology observed in human MG. Our data also demonstrated that inflammation is mandatory to reveal CXCL13 ability to recruit B cells and to induce tertiary lymphoid organ development. PMID:26771137

  20. Thymus involvement in myasthenia gravis: Epidemiological and clinical impacts of different self-tolerance breakdown mechanisms.

    PubMed

    Karni, Arnon; Asmail, Ali; Drory, Vivian E; Kolb, Hadar; Kesler, Anat

    2016-09-15

    The reasons for the abrogation of self-immunological tolerance in patients with myasthenia gravis (MG) may be different between those with concomitant thymic hyperplasia or thymoma, and those with no evidence of thymic involvement. We conducted a retrospective observational case series study to investigate the epidemiology as well as the clinical, serologic, and electromyographic (EMG) characteristics of individuals diagnosed as having MG. We found that the average age at MG onset of patients with either thymic hyperplasia or thymoma was much younger (by ~20years) than that of MG patients without thymic involvement. Thymic hyperplasia was more common in females than males. There were no differences in the rates of ocular MG vs. generalized MG among those three study groups. There were also no group differences in the rates of neuromuscular junction disfunction, as observed on EMG or by the results of serology tests for acetyl choline receptor antibody. Interestingly, only patients without thymic involvement had other autoimmune diseases, and most of them were females. The patients with other coexisting autoimmune disease had a similar age at MG onset as the other patients with no thymic involvement. These results shed light on the impact of epidemiological and clinical factors that result from different mechanisms of self-immunological tolerance breakdown that occurs in MG. PMID:27609276

  1. Systemic Lupus Erythematosus and Secondary Antiphospholipid Syndrome after Thymectomy for Myasthenia Gravis - A Case Report

    PubMed Central

    Miskovic, Rada; Plavsic, Aleksandra; Peric-Popadic, Aleksandra; Raskovic, Sanvila; Bogic, Mirjana

    2015-01-01

    INTRODUCTION: Systemic lupus erythematosus (SLE) and myasthenia gravis (MG) are autoimmune diseases that show some similarities: a higher incidence in young women, relapsing-remitting course and positive anti-nuclear antibodies (ANA). However, they are two different clinical syndromes, which can coexist or precede each other. Thymectomy is a therapeutic option for patients with severe MG or thymoma. There are many cases of SLE after thymectomy described in the literature, so the question arises whether thymectomy predisposes patients to SLE and what are imunopathogenetic mechanisms behind this process. CASE REPORT: We report a case of a patient who was diagnosed with SLE and secondary antiphospholipid syndrome (APS) 28 years after thymectomy for MG. Clinical picture of SLE was characterized by cutaneous and articular manifestations, polyserositis, lupus nephritis and immunological parameters showed positive ANA, anti-ds-DNA, excessive consumption of complement components, positive cryoglobulins. Clinical and laboratory immunological parameters for the diagnosis of secondary APS where also present. The patient was initially treated with glucocorticoids followed by mycophenolate mofetil. During one year follow-up patient was in a stable remission of SLE. CONCLUSION: Thymectomy for MG may predispose SLE development in some patients. Further studies are needed to better understand the connection between these two autoimmune diseases.

  2. Unmasking of myasthenia gravis during pegylated Alfa 2 a interferon and ribavirin therapy for chronic hepatitis C.

    PubMed

    Saleem, Ayesha

    2016-05-01

    Over last few decades, hepatitis C has emerged as a serious infection that has threatened the health and budgets of millions in the world. The objective of health professionals to treat it with recommended therapy of Alfa interferon and Ribavirin combination presents certain risks. One of the alarms is the ability of interferon to stimulate the production of autoantibodies in the body resulting in expression of autoimmune diseases in few who develop these antibodies. The case presented here is about unmasking of myasthenia gravis in a patient who received alfa interferon therapy for her chronic hepatitis C. Alfa interferon probably plays an important role in manifestation of the diseases in susceptible patients and all autoimmune diseases cannot be taken as mere side effects of the therapy. Clinicians need to be alert to pick up these diseases earlier so that the prompt management is possible. PMID:27183950

  3. An unexpected difficult intubation in a patient with myasthenia gravis undergoing video-assisted transcervical thymectomy

    PubMed Central

    Grasso, Nadia; Celestre, Chiara; Borrata, Francesco; Migliore, Marcello

    2013-01-01

    Although there are different methods to evaluate predictive parameters of difficult intubation in apparently normal patients, sometimes this event is unpredictable.We herein report a clinical case of difficult intubation during anaesthesia for video-assisted thymectomy in non-thymomatous myasthenia gravis. PMID:23749836

  4. Algaemia due to Prototheca wickerhamii in a patient with myasthenia gravis.

    PubMed Central

    Mohabeer, A J; Kaplan, P J; Southern, P M; Gander, R M

    1997-01-01

    Prototheca wickerhamii is a rare cause of systemic infection in humans. While some cases occur in previously healthy individuals, others are associated with a variety of preexisting diseases. Here we present, for the first time, a case of P. wickerhamii algaemia in a patient with myasthenia gravis. The patient was successfully treated with amphotericin B. PMID:9399541

  5. Disability and Functional Profiles of Patients with Myasthenia Gravis Measured with ICF Classification

    ERIC Educational Resources Information Center

    Leonardi, Matilde; Raggi, Alberto; Antozzi, Carlo; Confalonieri, Paolo; Maggi, Lorenzo; Cornelio, Ferdinando; Mantegazza, Renato

    2009-01-01

    The objective of this study is to describe functional profiles of patients with myasthenia gravis (MG), and the relationships among symptoms, activities and environmental factors (EF), by using WHO's International Classification of Functioning Disability and Health (ICF). Patients were consecutively enrolled at the Besta Institute of Milan, Italy.…

  6. Single fibre electromyographic studies in myasthenia gravis with repetitive nerve stimulation.

    PubMed Central

    Schwartz, M S; Stålberg, E

    1975-01-01

    A method is described for repetitive stimulation studies in myasthenia gravis using submaximal stimulation and single muscle fibre recording techniques. It was found that there were no impulse blockings due to neuromuscular transmission factors in normal subjects with 2 Hz stimulation, although there was a decrease or increase in the number of potentials which was caused by axonal stimulation factors. In myasthenia gravis a pathological picture was obtained, consisting of impulse blockings and facilitation at this rate in all of the eight patients studied, even those with only the ocular form of myasthenia and without surface decrement in the ADM. This technique allows study of both the minimally involved motor endplates and those with pronounced neuromuscular disturbances. Images PMID:1159439

  7. Cathepsin V is involved in the degradation of invariant chain in human thymus and is overexpressed in myasthenia gravis

    PubMed Central

    Tolosa, Eva; Li, Weijie; Yasuda, Yoshiyuki; Wienhold, Wolfgang; Denzin, Lisa K.; Lautwein, Alfred; Driessen, Christoph; Schnorrer, Petra; Weber, Ekkehard; Stevanovic, Stefan; Kurek, Raffael; Melms, Arthur; Brömme, Dieter

    2003-01-01

    Stepwise degradation of the invariant chain (Ii) is required for the binding of antigenic peptides to MHC class II molecules. Cathepsin (Cat) L in the murine thymus and Cat S in peripheral APCs have both been implicated in the last step of Ii degradation that gives rise to the class II–associated invariant chain peptides (CLIP). Cat V has been recently described as highly homologous to Cat L and exclusively expressed in human thymus and testis, but with no mouse orthologue. We report that Cat V is the dominant cysteine protease in cortical human thymic epithelial cells, while Cat L and Cat S seem to be restricted to dendritic and macrophage-like cells. Active Cat V in thymic lysosomal preparations was demonstrated by active-site labeling. Recombinant Cat V was capable of converting Ii into CLIP efficiently, suggesting that Cat V is the protease that controls the generation of αβ-CLIP complexes in the human thymus, in analogy to Cat L in mouse. Comparison of Cat V expression between thymi from patients with myasthenia gravis and healthy controls revealed a significantly higher expression level in the pathological samples, suggesting a potential involvement of this protease in the immunopathogenesis of myasthenia gravis, an autoimmune disease almost invariably associated with thymic pathology. PMID:12925692

  8. Azathioprine as a single immunosuppressive drug in the treatment of myasthenia gravis.

    PubMed

    Cosi, V; Lombardi, M; Erbetta, A; Piccolo, G

    1993-04-01

    We retrospectively evaluated results obtained from azathioprine (AZA) treatment on a selected sample of 40 patients affected by autoimmune myasthenia gravis (MG). Patients received AZA as a single immunosuppressive drug for at least 2 years. Twenty out of 40 patients received also a one-month course of cyclophosphamide (CP) before starting AZA. All patients started immunosuppressive treatment out of myasthenic crisis. After 3, 12 and 24 months of AZA treatment, 82.5%, 92.5% and 97.5% of the patients respectively showed improvement in functional state, disappearance of bulbar involvement, or both. The impressive percentage of short-term positive results did not seem influenced by pre-treatment by CP. Side effects included only minor and transitory gastrointestinal symptoms and reversible cytopenia. Although the patient population was either particularly suitable for AZA treatment or candidate to a better response, our data suggest that AZA might also have good short term effects in a subgroup of MG patients. PMID:8328322

  9. Collagen Q--a potential target for autoantibodies in myasthenia gravis.

    PubMed

    Zoltowska Katarzyna, Marta; Belaya, Katsiaryna; Leite, Maria; Patrick, Waters; Vincent, Angela; Beeson, David

    2015-01-15

    Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies targeting proteins expressed at the neuromuscular junction (NMJ). In most cases the targets are acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), or occasionally low-density lipoprotein receptor-related protein 4 (LRP4), but there is still a group of patients, often called seronegative MG (SNMG), with unknown antibody targets. One potential target is collagen Q (COLQ), which is restricted to the NMJ and is crucial for anchoring the NMJ-specific form of acetylcholinesterase (AChE). 415 serum samples with a clinical diagnosis of MG and 43 control samples were screened for the presence of COLQ autoantibodies using a cell-based assay (CBA) with HEK293 cells overexpressing COLQ at the cell surface. COLQ antibodies were detected in 12/415 MG sera and in one/43 control samples. Five of the COLQ-Ab+individuals were also positive for AChR-Abs and 2 for MuSK-Abs. Although the COLQ antibodies were only present at low frequency, and did not differ significantly from the small control cohort, further studies could address whether they modify the clinical presentation or the benefits of anti-cholinesterase therapy. PMID:25577314

  10. [Current status and future prospects of therapy for myasthenia gravis: considering thymectomy].

    PubMed

    Yoshikawa, Hiroaki; Iwasa, Kazuo; Takamori, Masaharu

    2011-07-01

    The benefits of thymectomy in non-thymomatous patients with myasthenia gravis (MG) remain controversial. The first detailed case of thymectomy in a patient with MG was reported in 1939, following which many cases were published. In 2000, Gronseth and Barohn reported the first meta-analysis of the effectiveness of thymectomy in MG patients without thymoma. They reviewed 28 papers systematically and reached these conclusions: (1) The benefit of thymectomy in non-thymomatous autoimmune MG has not been conclusively established, and (2) a well-designed controlled trial is essential. Following this report, Newsom-Davis et al. designed a thymectomy trial for non-thymomatous MG patients receiving prednisone (the MGTX study). Their study compared extended trans-sternal thymectomy (ETTX) combined with prednisone and prednisone alone groups with the aim to answer 3 questions: (1) Is the former more effective in improving myasthenic weakness? (2) Does the former require a lower total dose of prednisone, and thus decrease the likelihood of concurrent and long-term toxic effects? (3) Does the former enhance patients' quality of life by reducing adverse events and symptoms associated with the therapy? Currently, 67 centers, including our institute, are involved in this study. In total, 106 patients have been enrolled (the recruitment goal is 150). The patients are scheduled for a 5-year follow-up. The MGTX study will offer new information on the role of thymectomy in improving the quality of life of patients with MG. PMID:21747143

  11. Binding affinities of anti-acetylcholine receptor autoantibodies in myasthenia gravis

    SciTech Connect

    Bray, J.J.; Drachman, D.B.

    1982-01-01

    Antibodies directed against acetylcholine (ACh) receptors are present in the sera of nearly 90% of patients with myasthenia gravis (MG), and are involved in the pathogenesis of this autoimmune disease. However, the antibody titers measured by the standard radioimmunoassay correspond poorly with the clinical severity of the disease. To determine whether this disparity could be accounted for by differences in the binding affinities of anti-ACh receptor antibodies in different patients, we have measured the binding affinities of these autoantibodies in 15 sera from MG patients. The affinity constants (K/sub o/), as determined by Scatchard analysis, were all in the range of 10/sup 10/ M/sup -1/, comparable to the highest values reported in immunized animals. The affinity constants were truly representative of the population of autoantibodies detected by the radioimmunoassay, as shown by the remarkable linearity of the Scatchard plots (r/sup 2/>0.90) and the close correlation between the antibody titers determined by extrapolation of the Scatchard plots and by saturation analysis (r = 0.99; p < 0.001). There was only a 6-fold variation in affinity constants measured in this series of patients despite widely differing antibody titers and severity of the disease. Factors other than the titer and affinity of anti-ACh receptor antibodies may correlate better with the clinical manifestations of MG.

  12. Seropositive myasthenia and autoimmune autonomic ganglionopathy: cross reactivity or subclinical disease?

    PubMed

    Miglis, Mitchell G; Racela, Rikki; Kaufmann, Horacio

    2011-10-28

    Autoimmune autonomic ganglionopathy (AAG) and myasthenia gravis (MG) are both autoimmune channelopathies mediated by antibodies directed against nicotinic acetylcholine receptors. While both diseases target acetylcholine receptors, skeletal muscle and ganglionic receptor subtypes have key immunologic and genetic distinctions, and reports of patients with both AAG and MG are rare. We report a patient with antibody-confirmed AAG and elevated levels of ACh binding antibodies that did not meet clinical or electrodiagnostic criteria for MG. We presume that his skeletal muscle nAChR seropositivity was a false positive, perhaps due to the cross reactivity of the patient's ganglionic nAChR antibodies with skeletal nAChR subtypes. PMID:21745762

  13. Immunodominant regions for T helper-cell sensitization on the human nicotinic receptor alpha subunit in myasthenia gravis.

    PubMed Central

    Protti, M P; Manfredi, A A; Straub, C; Howard, J F; Conti-Tronconi, B M

    1990-01-01

    In myasthenia gravis an autoimmune response against the nicotinic acetylcholine receptor (AChR) occurs. The alpha subunit of the AChR contains both the epitope(s) that dominates the antibody response (main immunogenic region) and epitopes involved in T helper cell sensitization. In this study, overlapping synthetic peptides corresponding to the complete AChR alpha-subunit sequence were used to propagate polyclonal AChR-specific T helper cell lines from four myasthenic patients of different HLA types. Response of the T helper lines to the individual peptides was studied. Four immunodominant sequence segments were identified--i.e., residues 48-67, 101-120, 304-322, and 419-437. These regions did not include residues known to form the main immunogenic region or the cholinergic binding site, and they frequently contained sequence motifs that have been proposed to be related to T-epitope formation. Images PMID:2145582

  14. Laparoscopic Sleeve Gastrectomy in a Morbidly Obese Patient with Myasthenia Gravis: A Review of the Management

    PubMed Central

    Ballal, Megana; Straker, Tracey

    2015-01-01

    Myasthenia gravis, a disorder of neuromuscular transmission, presents a unique challenge to the perioperative anesthetic management of morbidly obese patients. This report describes the case of a 27-year-old morbidly obese woman with a past medical history significant for myasthenia gravis and fatty liver disease undergoing bariatric surgery. Anesthesia was induced with intravenous agents and maintained with an inhalational and balanced intravenous technique. The nondepolarizing neuromuscular blocker Cisatracurium was chosen so that no reversal agents were given. Neostigmine was not used to antagonize the effects of Cisatracurium. The goal of this approach was to reduce the risk of complications such as postoperative mechanical ventilation. The anesthetic and surgical techniques used resulted in an uneventful hospital course. Therefore, we can minimize perioperative risks and complications by adjusting the anesthetic plan based on the patient's physiology and comorbidities as well as the pharmacology of the drugs. PMID:26294914

  15. New onset of myasthenia gravis 10 years after proton beam therapy for thymoma.

    PubMed

    Karasaki, Takahiro; Murakawa, Tomohiro; Nagayama, Kazuhiro; Nitadori, Jun-Ichi; Anraku, Masaki; Kikuchi, Yoshinao; Shinozaki-Ushiku, Aya; Igaki, Hiroshi; Nakajima, Jun

    2016-05-01

    A 36-year-old woman underwent proton beam therapy for encapsulated type B1 thymoma for curative intent at 66 GyE. Radiographically partial response was achieved. Although the tumor size had been stable since that time, she developed systemic myasthenia gravis 10 years after the proton therapy. Extended thymectomy was performed. There were no adhesions between the tumor and the pericardium, and there were no adhesions also between the tumor and the sternum, probably due to the favor of Bragg peak effect. Extensive hyalinization with small foci of viable tumor cells showing degenerated type A-like morphology was observed in the resected tumor. Whether the viable cells represented recurrence with degenerative changes or de novo tumor formation was unable to be determined, and whether the viable cells were responsible for the onset of myasthenia gravis remained unclear. PMID:25301055

  16. Association of HLA-Bw46DR9 combination with juvenile myasthenia gravis in Chinese.

    PubMed Central

    Chen, W H; Chiu, H C; Hseih, R P

    1993-01-01

    One hundred and fifty two Chinese patients with myasthenia gravis in Taiwan were investigated for HLA-A, B, C and DR/DQ typing. HLA-Bw46 and DR9 frequencies were significantly increased in patients compared with the control group, and there was a decrease in DR3. Further analysis between different subgroups of patients showed Bw46 and DR9 were more significantly increased in the juvenile group than in the adult group. No single HLA allele was associated with either clinical type or thymic pathology, but there was an excess of BW46DR9 combination in both juvenile and ocular type patients. The Chinese population with myasthenia gravis is characterised by earlier age at onset, more ocular forms and less clinically severe illness than in whites, and these characteristics indicate a special subgroup that correlates with the strong Bw46DR9 association. PMID:8482958

  17. Memory in myasthenia gravis: neuropsychological tests of central cholinergic function before and after effective immunologic treatment.

    PubMed

    Glennerster, A; Palace, J; Warburton, D; Oxbury, S; Newsom-Davis, J

    1996-04-01

    There are reports of central cholinergic deficits in myasthenia gravis (MG) describing impaired performance on a variety of tests of memory with varying benefits from plasmapheresis. We tested 11 patients with symptomatic MG at the start of a trial of immunosuppressive treatment (prednisolone plus azathioprine or placebo) and again when in remission. The tests included the Logical Memory and Design Reproduction parts of the Wechsler Memory Scale, the Rey Auditory Verbal Learning Test, Peterson-Peterson task, and an auditory vigilance task. Muscle strength improved significantly over the period of treatment, but overall performance on tests of memory or attention did not. These results fail to substantiate reports of functionally significant and reversible central deficits in myasthenia gravis. PMID:8780106

  18. Myasthenia gravis as a 'stroke mimic'--it's all in the history.

    PubMed

    Shaik, Saiffuddin; Ul-Haq, Mian Ayaz; Emsley, Hedley C A

    2014-12-01

    An 85-year-old man presented to hospital as an emergency having difficulties with swallowing and speech. In the emergency department, he was assessed as having acute onset dysphagia and dysarthria in keeping with an acute stroke. Subsequently, it became apparent that although the symptoms were indeed of relatively acute onset, there was a clear description by the patient of fatigability and diurnal variation, prompting a working clinical diagnosis of myasthenia gravis. The patient followed a turbulent clinical course, and interpretation of investigation results proved not to be straightforward in the acute setting. Myasthenia gravis is an uncommon disorder but it is more common in the elderly. This case provides key learning points, particularly highlighting the value of prompt, accurate clinical assessment and the importance of adhering to the clinical diagnostic formulation. PMID:25468851

  19. [Merkel cell carcinoma of the skin in a patient with myasthenia gravis].

    PubMed

    Gianfreda, M; Caiffi, S; De Franceschi, T; Dodero, C; Durante, R; Faletti, P; Rebuttato, A; Schivo, A; Tassara, R

    2002-06-01

    Merkel cell carcinoma is a rare, aggressive neuroendocrine tumor of the skin commonly seen in the elderly on the head, neck and extremities, with a predisposition for local regional and distant spreading. A case of Merkel cell carcinoma occurred in a woman treated with immunosuppressive therapy for myasthenia gravis, is described and the possibility of a link between the immunosuppressive and/or oncogenic therapy and this tumor is suggested. PMID:12094153

  20. Colon Adenoma Implicating Myasthenia Gravis: A Case Report of a Patient with Postcolectomy Complications.

    PubMed

    Papachatzakis, Y; Tseliou, E; Tatouli, I; Dialoupi, I; Michas, F; Papadopoulou, E; Kousouris, D; Kontogiannis, S; Dimopoulos, M A

    2016-01-01

    We report the case of a 63-year-old patient with myasthenia gravis (MG) due to acetylcholine receptor antibodies (AChR) who underwent colectomy due to colon adenoma and developed myasthenic crisis and anastomosis leakage after surgery. The patient underwent two plasma exchanges, 4 and 6 days preoperatively, and received intravenous prednisolone and immunoglobulin infusion due to the crisis, which included primarily bulbar symptoms. The patient developed on the 10th postoperative day bowel obstruction symptoms and anastomosis leakage which required surgical repair and ileostomy. Bowel obstruction occurred in a patient with AChR related myasthenia after plasma exchange and during immunosuppression although it is more commonly reported in patients with thymoma related myasthenia. PMID:27610255

  1. Colon Adenoma Implicating Myasthenia Gravis: A Case Report of a Patient with Postcolectomy Complications

    PubMed Central

    Papachatzakis, Y.; Tatouli, I.; Dialoupi, I.; Michas, F.; Papadopoulou, E.; Kousouris, D.; Dimopoulos, M. A.

    2016-01-01

    We report the case of a 63-year-old patient with myasthenia gravis (MG) due to acetylcholine receptor antibodies (AChR) who underwent colectomy due to colon adenoma and developed myasthenic crisis and anastomosis leakage after surgery. The patient underwent two plasma exchanges, 4 and 6 days preoperatively, and received intravenous prednisolone and immunoglobulin infusion due to the crisis, which included primarily bulbar symptoms. The patient developed on the 10th postoperative day bowel obstruction symptoms and anastomosis leakage which required surgical repair and ileostomy. Bowel obstruction occurred in a patient with AChR related myasthenia after plasma exchange and during immunosuppression although it is more commonly reported in patients with thymoma related myasthenia. PMID:27610255

  2. Thymus cells in myasthenia gravis selectively enhance production of anti-acetylcholine-receptor antibody by autologous blood lymphocytes

    SciTech Connect

    Newsom-Davis, J.; Willcox, N.; Calder, L.

    1981-11-26

    We investigated the role of the thymus in 16 patients with myasthenia gravis without thymoma by studying the production of anti-acetylcholine-receptor antibody by thymic and blood lymphocytes cultured alone or together. In 10 responders (with the highest receptor-antibody titers in their plasma), cultured thymic cells spontaneously produced measurable receptor antibody. Receptor-antibody production by autologous blood lymphocytes was enhanced by the addition of responder's thymic cells, irradiated to abrogate antibody production and suppression (P<0.01). This enhancement was greater and more consistent than that by pokeweed mitogen; it depended on viable thymic cells, appeared to be selective for receptor antibody, and correlated with the ratio of thymic helper (OKT4-positive or OKT4+) to suppressor (OKT8+) T cells (P<0.01). These results suggest that myasthenic thymus contains cell-bound acetylcholine-receptor-like material or specific T cells (or both) that can aid receptor-antibody production. This may be relevant to the benefits of thymectomy in myasthenia and to the breakdown in self-tolerance in this and other autoimmune diseases.

  3. Myasthenia gravis: a long term follow‐up study of Swedish patients with specific reference to thymic histology

    PubMed Central

    Tsinzerling, Natalie; Lefvert, Ann‐Kari; Matell, Georg; Pirskanen‐Matell, Ritva

    2007-01-01

    Background Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. The majority of patients show abnormal thymic histology. Setting The study was performed at the Myasthenia Gravis Centre, Karolinska University Hospital, and at the Immunological Research Laboratory, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. Patients and methods Information was collected retrospectively from 1956 and prospectively from 1975 on clinical data, concomitant diseases, concentration of serum acetylcholine receptor antibodies (AChR‐abs), immunosuppressive treatment (IS) and response to it, in 537 patients of whom 326 were thymectomised. Follow‐up time was 1.5–50 years. Results Age at onset of MG increased from a median age of 24 years before 1975 to a median age of 61 years after 2000. Thymoma was found in 65, hyperplasia (HPL) in 185 and a normal thymus in 76 patients. The trans‐sternal surgical approach for thymectomy was used in 255 patients (78%). In five patients with thymoma, MG appeared after thymectomy. Of 537 patients, 466 (87%) had circulating AChR‐abs. IS was given to 300 (56%) patients, mostly those with thymoma (85%). In total, 441 patients (82%) showed an improvement. One‐third of patients with HPL, a quarter of those with thymoma, one‐fifth of those with a normal thymus and one‐seventh of those not operated on went into remission. Conclusion The prognosis for the majority of patients with MG is favourable, irrespective of thymic histology. The cause may be the use of immunomodulating therapy. PMID:17353257

  4. Molecular mimicry and myasthenia gravis. An autoantigenic site of the acetylcholine receptor alpha-subunit that has biologic activity and reacts immunochemically with herpes simplex virus.

    PubMed Central

    Schwimmbeck, P L; Dyrberg, T; Drachman, D B; Oldstone, M B

    1989-01-01

    The large majority of patients with the autoimmune disease myasthenia gravis characteristically have detectable antibodies against the acetylcholine receptor (AChR). We used synthetic peptides to identify antibodies in sera of myasthenia gravis patients reactive with the human acetylcholine receptor (HuAChR) alpha-subunit, residues 160-167. Affinity purification of these antibodies, using the HuAChR alpha-subunit 157-170 peptide immobilized on thiopropyl-Sepharose, yielded IgG antibodies that bound to the native AChR and inhibited the binding of alpha-bungarotoxin to the receptor. The HuAChR alpha-subunit 160-167 peptide demonstrated specific immunological cross-reactivity with a shared homologous domain on herpes simplex virus glycoprotein D, residues 286-293, by both binding and inhibition studies. Thus, HuAChR alpha-subunit, residues 160-167, elicits antibodies in myasthenic patients that binds to the native AChR protein and is capable of eliciting a biologic effect. Immunologic cross-reactivity of this "self" epitope with herpes simplex virus suggest that this virus may be associated with the initiation of some cases of myasthenia. Images PMID:2551924

  5. Oral administration of an immunodominant T-cell epitope downregulates Th1/Th2 cytokines and prevents experimental myasthenia gravis

    PubMed Central

    Baggi, Fulvio; Andreetta, Francesca; Caspani, Elisabetta; Milani, Monica; Longhi, Renato; Mantegazza, Renato; Cornelio, Ferdinando; Antozzi, Carlo

    1999-01-01

    The mucosal administration of the native antigen or peptide fragments corresponding to immunodominant regions is effective in preventing or treating several T cell–dependent models of autoimmune disease. No data are yet available on oral tolerance with immunodominant T-cell peptides in experimental autoimmune myasthenia gravis (EAMG), an animal model of B cell–dependent disease. We report that oral administration of the T-cell epitope α146-162 of the Torpedo californica acetylcholine receptor (TAChR) α-subunit suppressed T-cell responses to AChR and ameliorated the disease in C57Bl/6 (B6) mice. Protection from EAMG was associated with reduced serum Ab’s to mouse AChR and reduced AChR loss in muscle. The effect of Tα146-162 feeding was specific; treatment with a control peptide did not affect EAMG manifestations. The protective effect induced by peptide Tα146-162 was mediated by reduced production of IFN-γ, IL-2, and IL-10 by TAChR-reactive cells, suggesting T-cell anergy. TGF-β–secreting Th3 cells did not seem to be involved in tolerance induction. We therefore demonstrate that feeding a single immunodominant epitope can prevent an Ab-mediated experimental model of autoimmune disease. PMID:10545527

  6. Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the Guidelines of the German Neurological Society.

    PubMed

    Melzer, Nico; Ruck, Tobias; Fuhr, Peter; Gold, Ralf; Hohlfeld, Reinhard; Marx, Alexander; Melms, Arthur; Tackenberg, Björn; Schalke, Berthold; Schneider-Gold, Christiane; Zimprich, Fritz; Meuth, Sven G; Wiendl, Heinz

    2016-08-01

    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 PMID:26886206

  7. Two simultaneous autoimmune processes in a patient presenting with respiratory insufficiency

    PubMed Central

    Troy, Lauren; Hamor, Paul; Bleasel, Jane; Corte, Tamera

    2014-01-01

    The idiopathic inflammatory myopathies, including dermatomyositis, are uncommon acquired autoimmune diseases, sometimes associated with interstitial lung disease. Myasthenia gravis, a separate autoimmune disorder involving the neuromuscular junction, has some overlapping clinical features but has only rarely been reported to occur simultaneously within the same patient. Here we present the first reported case of concomitant dermatomyositis, myasthenia gravis, and interstitial lung disease. PMID:25473554

  8. Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

    PubMed Central

    Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

    2014-01-01

    Introduction Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. Case Report A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment. PMID:24926266

  9. Successful treatment of severe myasthenia gravis developed after allogeneic hematopoietic stem cell transplantation with plasma exchange and rituximab.

    PubMed

    Unal, Sule; Sag, Erdal; Kuskonmaz, Baris; Kesici, Selman; Bayrakci, Benan; Ayvaz, Deniz C; Tezcan, Ilhan; Yalnızoglu, Dilek; Uckan, Duygu

    2014-05-01

    Myasthenia gravis is among the rare complications after allogeneic hematopoietic stem cell transplantation and is usually associated with chronic GVHD. Herein, we report a 2-year and 10 months of age female with Griscelli syndrome, who developed severe myasthenia gravis at post-transplant +22nd month and required respiratory support with mechanical ventilation. She was unresponsive to cyclosporine A, methylprednisolone, intravenous immunoglobulin, and mycophenolate mofetil and the symptoms could only be controlled after plasma exchange and subsequent use of rituximab, in addition to cyclosporine A and mycophenolate mofetil maintenance. She is currently asymptomatic on the 6th month of follow-up. PMID:24307660

  10. Antigen-specific modulation of experimental myasthenia gravis: nasal tolerization with recombinant fragments of the human acetylcholine receptor alpha-subunit.

    PubMed

    Barchan, D; Souroujon, M C; Im, S H; Antozzi, C; Fuchs, S

    1999-07-01

    Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are antibody-mediated autoimmune diseases in which the nicotinic acetylcholine receptor (AcChoR) is the major autoantigen. The immune response in these diseases is heterogeneous and is directed to a wide variety of T and B cell epitopes of AcChoR. Candidate molecules for specific immunotherapy of MG should, therefore, have a broad specificity. We used recombinant fragments of the human AcChoR, encompassing the extracellular domain of the alpha-subunit, or shorter fragments derived from it, in experiments to modulate EAMG. We have demonstrated that intranasal administration of these recombinant fragments, which represent a major portion of epitopes involved in MG, prevents the induction of EAMG in rats and immunosuppresses an ongoing disease, as assessed by clinical symptoms, weight loss, and muscle AcChoR content. These effects on EAMG were accompanied by a marked reduction in the proliferative T-cell response and IL-2 production in response to AcChoR, in reduced anti-self AcChoR antibody titers and in an isotype switch of AcChoR-specific antibodies, from IgG2 to IgG1. We conclude that nasal tolerance induced by appropriate recombinant fragments of human AcChoR is effective in suppressing EAMG and might possibly be considered as a therapeutic modality for MG. PMID:10393952

  11. Antigen-specific modulation of experimental myasthenia gravis: Nasal tolerization with recombinant fragments of the human acetylcholine receptor α-subunit

    PubMed Central

    Barchan, Dora; Souroujon, Miriam C.; Im, Sin-Hyeog; Antozzi, Carlo; Fuchs, Sara

    1999-01-01

    Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are antibody-mediated autoimmune diseases in which the nicotinic acetylcholine receptor (AcChoR) is the major autoantigen. The immune response in these diseases is heterogeneous and is directed to a wide variety of T and B cell epitopes of AcChoR. Candidate molecules for specific immunotherapy of MG should, therefore, have a broad specificity. We used recombinant fragments of the human AcChoR, encompassing the extracellular domain of the α-subunit, or shorter fragments derived from it, in experiments to modulate EAMG. We have demonstrated that intranasal administration of these recombinant fragments, which represent a major portion of epitopes involved in MG, prevents the induction of EAMG in rats and immunosuppresses an ongoing disease, as assessed by clinical symptoms, weight loss, and muscle AcChoR content. These effects on EAMG were accompanied by a marked reduction in the proliferative T-cell response and IL-2 production in response to AcChoR, in reduced anti-self AcChoR antibody titers and in an isotype switch of AcChoR-specific antibodies, from IgG2 to IgG1. We conclude that nasal tolerance induced by appropriate recombinant fragments of human AcChoR is effective in suppressing EAMG and might possibly be considered as a therapeutic modality for MG. PMID:10393952

  12. Higher risk of myasthenia gravis in patients with thyroid and allergic diseases: a national population-based study.

    PubMed

    Yeh, Jiann-Horng; Kuo, Huang-Tsung; Chen, Hsuan-Ju; Chen, Yen-Kung; Chiu, Hou-Chang; Kao, Chia-Hung

    2015-05-01

    The aim of this study was to determine the risk of myasthenia gravis (MG) in patients with allergic or autoimmune thyroid disease in a large cohort representing 99% of the population in Taiwan. Data from the Taiwan National Health Insurance Database were used to conduct retrospective analyses. The study comprised 1689 adult patients with MG who were 4-fold frequency matched to those without MG by sex, age, and assigned the same index year. Multivariate logistic regression models were used to calculate the odds ratios and 95% confidence intervals for the association between allergic or autoimmune thyroid disease and MG. An increased subsequent risk of MG was observed in the patients with allergic conjunctivitis (AC), allergic rhinitis, Hashimoto thyroiditis, and Graves disease. The adjusted odds ratios (aORs) were 1.93 (1.71-2.18), 1.26 (1.09-1.45), 2.87 (1.18-6.97), and 3.97 (2.71-5.83), respectively. The aORs increased from 1.63 (1.43-1.85) in a patient with only 1 allergic or autoimmune thyroid disease to 2.09 (1.75-2.49) in a patient with 2 thyroid or allergic diseases to 2.82 (2.19-3.64) in a patient with ≥3 thyroid or allergic diseases. MG was associated with the cumulative effect of concurrent allergic and autoimmune thyroid disease with combined AC and Hashimoto thyroiditis representing the highest risk (aOR = 15.62 [2.88-87.71]). This population-based case-control study demonstrates the association between allergic or autoimmune thyroid disease and the risk of MG. The highest risk of subsequent MG was associated with combined AC and Hashimoto thyroiditis. PMID:26020387

  13. The Myotonic Plot Thickens: Electrical Myotonia in Antimuscle-Specific Kinase Myasthenia Gravis

    PubMed Central

    Magnussen, Marcus; Karakis, Ioannis; Harrison, Taylor B.

    2015-01-01

    Electrical myotonia is known to occur in a number of inherited and acquired disorders including myotonic dystrophies, channelopathies, and metabolic, toxic, and inflammatory myopathies. Yet, electrical myotonia in myasthenia gravis associated with antibodies against muscle-specific tyrosine kinase (MuSK) has not been previously reported. We describe two such patients, both of whom had a typical presentation of proximal muscle weakness with respiratory failure in the context of a significant electrodecrement in repetitive nerve stimulation. In both cases, concentric needle examination revealed electrical myotonia combined with myopathic motor unit morphology and early recruitment. These findings suggest that MuSK myasthenia should be included within the differential diagnosis of disorders with electrical myotonia. PMID:26770848

  14. Collagen Q is a key player for developing rational therapy for congenital myasthenia and for dissecting the mechanisms of anti-MuSK myasthenia gravis.

    PubMed

    Ohno, Kinji; Ito, Mikako; Kawakami, Yu; Ohtsuka, Kenji

    2014-07-01

    Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ) in the form of asymmetric AChE (AChE/ColQ). We exploited the proprietary NMJ-targeting signals of ColQ to treat congenital myasthenia and to explore the mechanisms of autoimmune myasthenia gravis (MG). Mutations in COLQ cause congenital endplate AChE deficiency (CEAD). First, a single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq−/− mice normalized motor functions, synaptic transmission, and partly the NMJ ultrastructure. Additionally, injection of purified recombinant AChE/ColQ protein complex into gluteus maximus accumulated AChE in non-injected forelimbs. Second, MuSK antibody-positive MG accounts for 5-15 % of MG. In vitro overlay of AChE/ColQ to muscle sections of Colq−/− mice, as well as in vitro plate-binding of MuSK to ColQ, revealed thatMuSK-IgG blocks binding of ColQ to MuSK in a dose-dependent manner. Passive transfer of MuSK-IgG to wild-type mice markedly reduced the size and intensity of ColQ signals at NMJs. MuSK-IgG thus interferes with binding of ColQ to MuSK. Elucidation of molecular mechanisms of specific binding of ColQ to NMJ enabled us to ameliorate devastating myasthenic symptoms of Colq−/− mice and also to reveal underlying mechanisms of anti-MuSK-MG. PMID:24234034

  15. Cholinergic neuromuscular hyperactivity in patients with myasthenia gravis seropositive for MuSK antibody.

    PubMed

    Punga, Anna Rostedt; Flink, Roland; Askmark, Håkan; Stålberg, Erik V

    2006-07-01

    A 75-year-old man with severe oculobulbar myasthenia gravis (MG) treated with acetylcholine esterase inhibitors (AChEIs) was found to have muscle-specific tyrosine kinase (MuSK) antibodies. Neurophysiological examination displayed extra repetitive discharges after the compound motor action potential (CMAP) at low-frequency stimulation, possibly triggered by AChEI. This indicates an abnormal sensitivity to acetylcholine in patients with MuSK antibodies and may be a useful indicator of the adverse effect of AChEI treatment in these patients. PMID:16453324

  16. Major motor-functional determinants associated with poor self-reported health-related quality of life in myasthenia gravis patients.

    PubMed

    Cioncoloni, David; Casali, Stefania; Ginanneschi, Federica; Carone, Marisa; Veronica, Boni; Rossi, Alessandro; Giannini, Fabio

    2016-05-01

    Myasthenia gravis (MG) is an autoimmune neuromuscular disorder in which disabling muscle weakness may affect health-related quality of life (HRQoL). The aim of this study was to investigate which common motor-functional deficits and corresponding severity are most determinant of poor HRQoL in these patients. In 41 patients, the dichotomized first item of the Italian Myasthenia Gravis Questionnaire (IMGQ), categorizing patients who report "good" and "poor" HRQoL, was chosen as dependent-outcome variable. All items composing the myasthenia gravis-specific scale (MG-ADL), i.e. talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to rise from chair, double vision, and eyelid droop were acquired as independent variables and dichotomized. Stepwise backward LR multivariable logistic regression analysis was performed. In addition, the main characteristics of patients were compared. MG-ADL items "chewing" ≥1, i.e. "fatigue chewing solid food", and "breathing" ≥2, i.e. "shortness of breath at rest" proved to be significant determinants. Higher dose of corticosteroid therapy was significantly (p = 0.027; r s  = -0.35), correlated with poor HRQoL. At diagnosis, a decremental response to repetitive nerve stimulation (RNS) from the abductor pollicis brevis was significantly more frequent in patients with poor HRQoL. In conclusion, impaired "chewing" and "breathing" functions indicate the need for careful planning of rehabilitation, re-education and patient management. Moreover, decremental response to RNS at diagnosis may identify patients at risk for poor HRQoL. PMID:27038315

  17. Genome-Wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A and Identification of ZBTB10 and Three Distinct HLA Associations

    PubMed Central

    Seldin, Michael F; Alkhairy, Omar K; Lee, Annette T; Lamb, Janine A; Sussman, Jon; Pirskanen-Matell, Ritva; Piehl, Fredrik; Verschuuren, Jan J G M; Kostera-Pruszczyk, Anna; Szczudlik, Piotr; McKee, David; Maniaol, Angelina H; Harbo, Hanne F; Lie, Benedicte A; Melms, Arthur; Garchon, Henri-Jean; Willcox, Nicholas; Gregersen, Peter K; Hammarstrom, Lennart

    2015-01-01

    To investigate the genetics of late-onset myasthenia gravis (LOMG), we conducted a genome-wide association study imputation of >6 million single nucleotide polymorphisms (SNPs) in 532 LOMG cases (anti–acetylcholine receptor [AChR] antibody positive; onset age ≥50 years) and 2,128 controls matched for sex and population substructure. The data confirm reported TNFRSF11A associations (rs4574025, P = 3.9 × 10−7, odds ratio [OR] 1.42) and identify a novel candidate gene, ZBTB10, achieving genome-wide significance (rs6998967, P = 8.9 × 10−10, OR 0.53). Several other SNPs showed suggestive significance including rs2476601 (P = 6.5 × 10−6, OR 1.62) encoding the PTPN22 R620W variant noted in early-onset myasthenia gravis (EOMG) and other autoimmune diseases. In contrast, EOMG-associated SNPs in TNIP1 showed no association in LOMG, nor did other loci suggested for EOMG. Many SNPs within the major histocompatibility complex (MHC) region showed strong associations in LOMG, but with smaller effect sizes than in EOMG (highest OR ~2 versus ~6 in EOMG). Moreover, the strongest associations were in opposite directions from EOMG, including an OR of 0.54 for DQA1*05:01 in LOMG (P = 5.9 × 10−12) versus 2.82 in EOMG (P = 3.86 × 10−45). Association and conditioning studies for the MHC region showed three distinct and largely independent association peaks for LOMG corresponding to (a) MHC class II (highest attenuation when conditioning on DQA1), (b) HLA-A and (c) MHC class III SNPs. Conditioning studies of human leukocyte antigen (HLA) amino acid residues also suggest potential functional correlates. Together, these findings emphasize the value of subgrouping myasthenia gravis patients for clinical and basic investigations and imply distinct predisposing mechanisms in LOMG. PMID:26562150

  18. Stable Expression of Human Muscle-Specific Kinase in HEp-2 M4 Cells for Automatic Immunofluorescence Diagnostics of Myasthenia Gravis

    PubMed Central

    George, Sandra; Paulick, Silvia; Knütter, Ilka; Röber, Nadja; Hiemann, Rico; Roggenbuck, Dirk; Conrad, Karsten; Küpper, Jan-Heiner

    2014-01-01

    Muscle-specific kinase (MuSK) belongs to the nicotinic acetylcholine receptor complex which is targeted by pathogenic autoantibodies causing Myasthenia gravis. While up to 95% of patients with generalized Myasthenia gravis were shown to be positive for acetylcholine receptor-specific autoantibodies, up to 70% of the remaining patients develop autoantibodies against MuSK. Discrimination of the autoantibody specificity is important for therapy of Myasthenia gravis. Recently, the new automatic fluorescence assessment platform AKLIDES has been developed for immunofluorescence-based diagnostics of autoimmune diseases. In order to establish an AKLIDES procedure for the detection of MuSK-specific autoantibodies (anti-MuSK), we developed a recombinant HEp-2 cell clone expressing the human MuSK cDNA. Here we show at the mRNA and protein level that the cell clone HEp-2 M4 stably expresses human MuSK. We provide evidence for a localization of MuSK at the cell membrane. Using cell clone HEp-2 M4 on the AKLIDES system, we investigated 34 patient sera that were previously tested anti-MuSK positive by radioimmunoassay as positive controls. As negative controls, we tested 29 acetylcholine receptor-positive but MuSK-negative patient sera, 30 amytrophic lateral sclerosis (ALS) patient sera and 45 blood donors. HEp-2 M4 cells revealed a high specificity for the detection of MuSK autoantibodies from 25 patient sera assessed by a specific pattern on HEp-2 M4 cells. By using appropriate cell culture additives, the fraction of cells stained positive with anti-MuSK containing sera can be increased from 2–16% to 10–48%, depending on the serum. In conclusion, we provide data showing that the novel recombinant cell line HEp-2 M4 can be used to screen for anti-MuSK with the automatic AKLIDES system. PMID:24416182

  19. Myasthenia Gravis, Lambert-Eaton Myasthenic Syndrome & Congenital Myasthenic Syndromes

    MedlinePlus

    ... In most cases of MG, the immune system origins of MG have gradually unfolded, targets the acetylcholine ... is a rare autoimmune disease whose symptoms and origins are some- what similar to those of MG. ...

  20. Membranous nephropathy, leiomyoma and autoimmune myasthenia: more than a coincidence?

    PubMed

    Calviño, Jesus; Adeva, Magdalena; Sobrido, Maria-Jesus

    2012-12-01

    Membranous nephropathy (MN) has been associated with several infectious, immunological and malignant conditions, but had only rarely been reported with malignant and other immune disorders in the same patient. We describe the case of a 56-year-old male with MN who was also diagnosed with a gastrointestinal stromal tumour (GIST), myasthenia gravis (MG) and thymic hyperplasia. Thus, we report here for the first time the coincidence of these conditions in the same patient. There was a recurrence of nephrotic syndrome without impairment of renal function 5 years after removal of the GIST (3 years after thymectomy). The possible basis for the relationship between these diseases is discussed, and some common genetic and immune physiopathological pathways are hypothesized. PMID:26069802

  1. Membranous nephropathy, leiomyoma and autoimmune myasthenia: more than a coincidence?

    PubMed Central

    Calviño, Jesus; Adeva, Magdalena; Sobrido, Maria-Jesus

    2012-01-01

    Membranous nephropathy (MN) has been associated with several infectious, immunological and malignant conditions, but had only rarely been reported with malignant and other immune disorders in the same patient. We describe the case of a 56-year-old male with MN who was also diagnosed with a gastrointestinal stromal tumour (GIST), myasthenia gravis (MG) and thymic hyperplasia. Thus, we report here for the first time the coincidence of these conditions in the same patient. There was a recurrence of nephrotic syndrome without impairment of renal function 5 years after removal of the GIST (3 years after thymectomy). The possible basis for the relationship between these diseases is discussed, and some common genetic and immune physiopathological pathways are hypothesized. PMID:26069802

  2. [Reversal of rocuronium induced neuromuscular block with sugammadex in a patient with myasthenia gravis].

    PubMed

    Nakamori, Erisa; Nitahara, Keiichi; Sugi, Yasuyuki; Katori, Kiyoshi; Matsuzaki, Akiko; Higa, Kazuo

    2013-08-01

    We report a patient with myasthenia gravis whose rocuronium induced neuromuscular block was reversed with sugammadex. A 26-year-old man, 175 cm and 76 kg, with myasthenia gravis, was scheduled for extended thymectomy under general anesthesia. An epidural catheter was inserted at the T5-6 interspace before induction of general anesthesia. Anesthesia was induced with propofol and remifentanil. Rocuronium was given in divided doses to obtain > 95% neuromuscular block to intubate the trachea. The ED50 and ED95 of rocuronium for this patient were 0.18 mg x kg(-1) and 0.39 mg x kg(-1), respectively. The values were similar to the ED50 and ED95 of rocuronium for normal patients. General anesthesia was maintained with propofol and remifentanil. Additional doses of rocuronium were given intermittently. Sugammadex, 2 mg x kg(-1), was given at the end of the surgery. The train-of-four ratio reached 93% 105 sec later. His postoperative course was uneventful. PMID:23984578

  3. Serum uric acid levels in patients with myasthenia gravis are inversely correlated with disability

    PubMed Central

    Yang, Dehao; Weng, Yiyun; Lin, Haihua; Xie, Feiyan; Yin, Fang; Lou, Kangliang; Zhou, Xuan; Han, Yixiang; Li, Xiang

    2016-01-01

    Uric acid (UA), the final product of purine metabolism, has been reported to be reduced in patients with various neurological disorders and is considered to be a possible indicator for monitoring the disability and progression of multiple sclerosis. However, it remains unclear whether there is a close relationship between UA and myasthenia gravis (MG), or whether UA is primarily deficient or secondarily reduced because of its peroxynitrite scavenging activity. We investigated the correlation between serum UA levels and the clinical characteristics of MG. We assessed 338 serum UA levels obtained in 135 patients with MG, 47 patients with multiple sclerosis, and 156 healthy controls. In addition, we compared serum UA levels when MG patients were stratified according to disease activity and classifications performed by the Myasthenia Gravis Foundation of America, age of onset, duration, and thymus histology (by means of MRI or computed tomography). MG patients had significantly lower serum UA levels than the controls (P<0.001). Moreover, UA levels in patients with MG were inversely correlated with disease activity and disease progression (P=0.013). However, UA levels did not correlate significantly with disease duration, age of onset, and thymus histology. Our findings suggest that serum level of UA was reduced in patients with MG and serum UA might be considered a surrogate biomarker of MG disability and progression. PMID:26836463

  4. Mechanisms of acetylcholine receptor loss in myasthenia gravis.

    PubMed Central

    Drachman, D B; Adams, R N; Stanley, E F; Pestronk, A

    1980-01-01

    The fundamental abnormality affecting the neuromuscular junctions of myasthenic patients is a reduction of available AChRs, due to an autoimmune attack directed against the receptors. Antibodies to AChR are present in most patients, and there is evidence that they have a predominant pathogenic role in the disease, aided by complement. The mechanism of antibody action involves acceleration of the rate of degradation of AChRs, attributable to cross-linking of the receptors. In addition, antibodies may block AChRs, and may participate in producing destructive changes, perhaps in conjunction with complement. The possibility that cell-mediated mechanisms may play a role in the autoimmune responses of some myasthenic patients remains to be explored. Although the target of the autoimmune attack in myasthenic patients is probably always the acetylcholine receptors, it is not yet clear which of these immune mechanisms are most important. It is likely that the relative role of each mechanism varies from patient to patient. One of the goals of future research will be to identify the relative importance of each of these mechanisms in the individual patient, and to tailor specific immunotherapeutic measures to the abnormalities found. PMID:6249894

  5. T-cell receptor V sub. alpha. and C sub. alpha. alleles associated with multiple sclerosis and myasthenia gravis

    SciTech Connect

    Oksenberg, J.R.; Cavalli-Sforza, L.L.; Steinman, L. ); Sherritt, M.; Bernard, C.C. ); Begovich, A.B.; Erlich, H.A. )

    1989-02-01

    Polymorphic markers in genes encoding the {alpha} chain of the human T-cell receptor (TcR) have been detected by Southern blot analysis in Pss I digests. Polymorphic bands were observed at 6.3 and 2.0 kilobases (kb) with frequencies of 0.30 and 0.44, respectively, in the general population. Using the polymerase chain reaction (PCR) method, the authors amplified selected sequences derived from the full-length TcR {alpha} cDNA probe. These PcR products were used as specific probes to demonstrate that the 6.3-kb polymorphic fragment hybridizes to the variable (V)-region probe and the 2.0-kb fragment hybridizes to the constant (C)-region probe. Segregation of the polymorphic bands was analyzed in family studies. To look for associations between these markers and autoimmune diseases, the authors have studied the restriction fragment length polymorphism distribution of the Pss I markers in patients with multiple sclerosis, myasthenia gravis, and Graves disease. Significant differences in the frequency of the polymorphic V{sub {alpha}} and C{sub {alpha}} markers were identified between patients and healthy individuals.

  6. [Recent advance in research for myasthenia gravis, in relation to various antibodies affecting synaptic structure and function].

    PubMed

    Takamori, Masaharu

    2009-11-01

    Autoantibodies impair acetylcholine receptor (AChR) in myasthenia gravis (MG) and P/Q-type voltage-gated calcium channel (VGCC) in Lambert-Eaton myasthenic syndrome (LEMS). (1) Some of MG and LEMS patients are "seronegative" for respective antibodies or modified by antibodies that recognize other proteins than AChR and VGCC such as MuSK, AChR allosteric site, membrane Na+ channel and ryanodine receptor-1 (RyR1) in MG, and synaptotagmin-1 in LEMS. (2) Autoimmune responses affect the proteins participating in the mechanisms to compensate for synaptic disorders on the basis of presynaptic Ca2+ homeostasis provided by VGCC and non-VGCC (receptor-operated TRPCs): they act as enhancers of Ca(2+) -mediated ACh release via phospholipase C signaling pathways including M1-type presynaptic muscarinic AChR, neurotrophin receptor (TrkB), and fast-mode of synaptic vesicle recycling. (3) The pathophysiology contributive to contractile fatigue in MG includes RyR1 and also TRPC3. The TRPC3 also forms a complex with STIM1 and Orail to make up for Ca2+ after sarcoplasmic Ca2+ release. The prevalent detection of anti-TRPC3 antibodies in MG with thymoma could affect muscle contractile machineries in addition to anti-RyR1-induced affection. (4) When one faces "seronegative" MG, one should be cautious to conformation-specific antibodies and also congenital myasthenic syndromes. PMID:20030211

  7. Blood Transcriptome Profiling in Myasthenia Gravis Patients to Assess Disease Activity: A Pilot RNA-seq Study

    PubMed Central

    Park, Kee Hong; Jung, Junghee; Lee, Jung-Hee

    2016-01-01

    Myasthenia gravis (MG) is an antibody-mediated autoimmune disease characterized by exertional weakness. There is no biomarker to reflect disease activity and guide treatment decision. Here, we reported a pilot blood transcriptome study using RNA sequencing (RNA-seq) that identified differences of 5 samples in active status and 5 in remission from 8 different patients and 2 patients provided samples for both active and remission phase. We found a total of 28 differentially expressed genes (DEGs) possibly related to disease activity (23 up-regulated and 5 down-regulated). The DEGs were enriched for the cell motion and cell migration processes in which included were ICAM1, CCL3, S100P and GAB2. The apoptosis and cell death pathway was also significantly enriched, which includes NFKBIA, ZC3H12A, TNFAIP3, and PPP1R15A. Our result suggests that transcript abundance profiles of the genes involved in cell trafficking and apoptosis may be a molecular signature of the disease activity in MG patients. PMID:26924932

  8. Flow Cytofluorimetric Analysis of Anti-LRP4 (LDL Receptor-Related Protein 4) Autoantibodies in Italian Patients with Myasthenia Gravis

    PubMed Central

    Marino, Mariapaola; Scuderi, Flavia; Samengo, Daniela; Saltelli, Giorgia; Maiuri, Maria Teresa; Shen, Chengyong; Mei, Lin; Sabatelli, Mario; Pani, Giovambattista; Antonini, Giovanni; Evoli, Amelia; Bartoccioni, Emanuela

    2015-01-01

    Background Myasthenia gravis (MG) is an autoimmune disease in which 90% of patients have autoantibodies against the muscle nicotinic acetylcholine receptor (AChR), while autoantibodies to muscle-specific tyrosine kinase (MuSK) have been detected in half (5%) of the remaining 10%. Recently, the low-density lipoprotein receptor-related protein 4 (LRP4), identified as the agrin receptor, has been recognized as a third autoimmune target in a significant portion of the double sero-negative (dSN) myasthenic individuals, with variable frequency depending on different methods and origin countries of the tested population. There is also convincing experimental evidence that anti-LRP4 autoantibodies may cause MG. Methods The aim of this study was to test the presence and diagnostic significance of anti-LRP4 autoantibodies in an Italian population of 101 myasthenic patients (55 dSN, 23 AChR positive and 23 MuSK positive), 45 healthy blood donors and 40 patients with other neurological diseases as controls. All sera were analyzed by a cell-based antigen assay employing LRP4-transfected HEK293T cells, along with a flow cytofluorimetric detection system. Results We found a 14.5% (8/55) frequency of positivity in the dSN-MG group and a 13% frequency of co-occurrence (3/23) in both AChR and MuSK positive patients; moreover, we report a younger female prevalence with a mild form of disease in LRP4-positive dSN-MG individuals. Conclusion Our data confirm LRP4 as a new autoimmune target, supporting the value of including anti-LRP4 antibodies in further studies on Myasthenia gravis. PMID:26284792

  9. Nivolumab for the treatment of malignant melanoma in a patient with pre-existing myasthenia gravis

    PubMed Central

    Maeda, Osamu; Yokota, Kenji; Atsuta, Naoki; Katsuno, Masahisa; Akiyama, Masashi; Ando, Yuichi

    2016-01-01

    ABSTRACT A 79-year-old man with lymph node recurrence of malignant melanoma received nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody. He had pre-existing ocular myasthenia gravis (MG) and a continued small amount of corticosteroid. Grade 3 creatine phosphokinase elevation appeared after two doses of nivolumab, and the treatment was postponed until it improved to grade 1. After three doses of nivolumab, he experienced diplopia and facial muscle weakness which were consistent with an acute exacerbation of MG, and the symptoms relieved without additional treatment for MG. He achieved shrinkage of metastasis after ten doses of nivolumab. Although a case who died due to MG after administration of nivolumab was reported recently, pre-existing MG is considered not to be always a contraindication of nivolumab. PMID:27019533

  10. [A case of myasthenia gravis with transient taste disorders followed by aplastic anemia after thymectomy].

    PubMed

    Osada, Osamu; Iwasaki, Akira; Nakahashi, Hirotaka; Kim, Yoshitora; Kaneko, Kou

    2016-01-01

    A 45-year-old man was admitted to our hospital because of taste disorders in March 2014. He exhibited cervical muscle weakness and left eye ptosis, which responded to Tensilon test, and was diagnosed with myasthenia gravis (MG). He developed aspiration pneumonia and myasthenic crisis, which was treated with intravenous immunoglobulin and steroid pulse therapy. All symptoms disappeared. Oral administration of prednisolone and tacrolimus was started. Chest CT revealed thymoma and extended thymectomy was performed in May 2014. In December 2014, seven months after the thymectomy, hematological examination showed pancytopenia including severe neutropenia. We diagnosed his illness as aplastic anemia (AA). Cyclosporine therapy with transfusion was administerd and led to reticulocyte count recovery. Since May 2015, hemoglobin recovery reached a blood transfusion free period. To our knowledge, this is the first case report with the patient supposed of relationship among taste disorders, AA and thymoma-associated MG. PMID:26876109

  11. Intravenous immunoglobulin-induced hemolytic anemia after thoracoscopic thymectomy for myasthenia gravis.

    PubMed

    Tsukada, Hisashi; Sunkara, Rajitha; Chi, Dorcas Doja; Keogh, Deirdre; Gaissert, Henning

    2014-06-01

    A 24-year-old woman underwent video-assisted thoracoscopic thymectomy for Osserman IIB myasthenia gravis (MG). In preparation for thymectomy, high-dose intravenous immunoglobulin (IVIG) was administered 1 week before the surgical procedure. After uneventful thoracoscopic thymectomy, the postoperative hemoglobin value decreased from 12.1 mg/dL to 8.2 mg/dL. A diagnosis of IVIG-associated hemolytic anemia was made based on a peripheral smear with numerous spherocytes, a positive direct antiglobulin test result, and increased reticulocyte count. Hemoglobin levels after IVIG administration should be monitored closely before and after elective surgical procedures to identify severe anemia. Transfusion of type-matched blood should be avoided and risk factors understood. PMID:24882299

  12. Rapid Return of Spontaneous Respiration after General Anesthesia with Sugammadex in a Patient with Myasthenia Gravis

    PubMed Central

    Kim, Raing Kyu; Kim, Soon Yul

    2016-01-01

    Myasthenia gravis causes weakness and fatigue of the skeletal muscles, including respiratory muscles. When immobile surgical fields are needed, neuromuscular blocking agents (NMBAs) are often administered to block muscle activity, leading to an immobile surgical field and respiratory arrest. Acetylcholinesterase inhibitors are administered to reverse the muscle block, promoting spontaneous respiration for patient recovery. If immobile surgical fields are required in myasthenic patient operations, NMBAs should be administered. However, recovery from NMBAs using acetylcholinesterase inhibitors might be delayed in myasthenic patients due to their intake of medicines that already inhibit cholinesterase, resulting in a delay in spontaneous respiration. Sugammadex is a recently introduced medicine that reverses muscle blocks through a different mechanism from acetylcholinesterase inhibitors and can be administered to facilitate the return of spontaneous respiration in myasthenic patients. Our experience of the rapid return to spontaneous respiration of a myasthenic patient with Sugammadex is reported in this paper. PMID:27358839

  13. The psychosocial impact of ptosis as a symptom of Myasthenia Gravis: a qualitative study.

    PubMed

    Richards, Hollie Sarah; Jenkinson, Elizabeth; Rumsey, Nichola; Harrad, Richard A

    2014-08-01

    The aim of this qualitative study was to investigate the psychosocial impact of ptosis as a symptom of Myasthenia Gravis (MG). Participants were recruited from a MG patient group on Facebook. 166 participants answered a series of open ended questions examining the impact of ptosis, and responses were analysed using Inductive Thematic Analysis, which revealed four main themes. The first highlighted the extent to which ptosis impacted negatively on psychosocial functioning. The second related to ways in which ptosis can be framed in a positive way, eg, as a believable symptom. The final two themes revealed the complex inter-relationships between functional and appearance-related impacts, and a desire from many participants for health care professionals to provide more support directly related to their ptosis. This study suggests that ptosis impacts in ways not currently recognized in literature and practice. PMID:24832459

  14. Guidelines for pre-clinical assessment of the acetylcholine receptor--specific passive transfer myasthenia gravis model-Recommendations for methods and experimental designs.

    PubMed

    Kusner, Linda L; Losen, Mario; Vincent, Angela; Lindstrom, Jon; Tzartos, Socrates; Lazaridis, Konstantinos; Martinez-Martinez, Pilar

    2015-08-01

    Antibodies against the muscle acetylcholine receptor (AChR) are the most common cause of myasthenia gravis (MG). Passive transfer of AChR antibodies from MG patients into animals reproduces key features of human disease, including antigenic modulation of the AChR, complement-mediated damage of the neuromuscular junction, and muscle weakness. Similarly, AChR antibodies generated by active immunization in experimental autoimmune MG models can subsequently be passively transferred to other animals and induce weakness. The passive transfer model is useful to test therapeutic strategies aimed at the effector mechanism of the autoantibodies. Here we summarize published and unpublished experience using the AChR passive transfer MG model in mice, rats and rhesus monkeys, and give recommendations for the design of preclinical studies in order to facilitate translation of positive and negative results to improve MG therapies. PMID:25743217

  15. Life-threatening misdiagnosis of bulbar onset myasthenia gravis as a motor neuron disease: How much can one rely on exaggerated deep tendon reflexes

    PubMed Central

    Basiri, Keivan; Ansari, Behnaz; Okhovat, Ali Asghar

    2015-01-01

    The autoimmune disease myasthenia gravis (MG), can mimic a variety of neurological disorders leading to a delay in diagnosis and treatment. On occasions, misdiagnosis of MG could lead to unnecessary therapeutic interventions. We report the case of a 50 year-old man, in whom MG was mistaken for motor neuron disease (MND). Subsequently, correct diagnosis and optimal management resulted in saving his life and significant improvement in his functional status. We discuss the importance of considering MG as one of the potential differential diagnoses among cases of new onset or recurrent unexplained bulbar symptoms, despite exaggerated deep tendon reflexes. Also, a literature review on the misdiagnosis of MG and the potential pitfalls in MG diagnosis are discussed. PMID:25802827

  16. The clinical absolute and relative scoring system-a quantitative scale measuring myasthenia gravis severity and outcome used in the traditional Chinese medicine.

    PubMed

    Liu, Guo-Chao; Gao, Bu-Lang; Yang, Hong-Qi; Qi, Guo-Yan; Liu, Peng

    2014-10-01

    Myasthenia gravis (MG) is a chronic autoimmune disease caused by autoantigen against the nicotine acetylcholine receptor at the neuromuscular junction. With modern treatment facilities, the treatment effect and outcome for MG has been greatly improved with MG and non-MG patients enjoying the same life expectancy. Many classifications of disease distribution and severity have been set up and tested all over the world, mainly in the western world. However, the absolute and relative scoring system for evaluating the severity and treatment effect of MG in China where traditional Chinese medicine (TCM) has been practiced for thousands of years has not been introduced worldwide. The TCM has achieved a great success in the treatment of MG in the country with a huge population. This article serves to introduce this scoring system to the world. PMID:25440379

  17. Altered Active Zones, Vesicle Pools, Nerve Terminal Conductivity, and Morphology during Experimental MuSK Myasthenia Gravis

    PubMed Central

    Patel, Vishwendra; Oh, Anne; Voit, Antanina; Sultatos, Lester G.; Babu, Gopal J.; Wilson, Brenda A.; Ho, Mengfei; McArdle, Joseph J.

    2014-01-01

    Recent studies demonstrate reduced motor-nerve function during autoimmune muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG). To further understand the basis of motor-nerve dysfunction during MuSK-MG, we immunized female C57/B6 mice with purified rat MuSK ectodomain. Nerve-muscle preparations were dissected and neuromuscular junctions (NMJs) studied electrophysiologically, morphologically, and biochemically. While all mice produced antibodies to MuSK, only 40% developed respiratory muscle weakness. In vitro study of respiratory nerve-muscle preparations isolated from these affected mice revealed that 78% of NMJs produced endplate currents (EPCs) with significantly reduced quantal content, although potentiation and depression at 50 Hz remained qualitatively normal. EPC and mEPC amplitude variability indicated significantly reduced number of vesicle-release sites (active zones) and reduced probability of vesicle release. The readily releasable vesicle pool size and the frequency of large amplitude mEPCs also declined. The remaining NMJs had intermittent (4%) or complete (18%) failure of neurotransmitter release in response to 50 Hz nerve stimulation, presumably due to blocked action potential entry into the nerve terminal, which may arise from nerve terminal swelling and thinning. Since MuSK-MG-affected muscles do not express the AChR γ subunit, the observed prolongation of EPC decay time was not due to inactivity-induced expression of embryonic acetylcholine receptor, but rather to reduced catalytic activity of acetylcholinesterase. Muscle protein levels of MuSK did not change. These findings provide novel insight into the pathophysiology of autoimmune MuSK-MG. PMID:25438154

  18. Selective response to rituximab in a young child with MuSK-associated myasthenia gravis.

    PubMed

    Govindarajan, Raghav; Iyadurai, Stanley J; Connolly, Anne; Zaidman, Craig

    2015-08-01

    Neuromuscular junction disorders in children are either genetic, such as congenital myasthenic syndrome, or autoimmune with circulating antibodies most commonly against acetylcholine receptors. There is limited experience recognizing and treating children with myasthenia associated with muscle-specific tyrosine kinase antibodies. We report a seven-year-old child with intermittent esotropia since age 3 months, and two years of progressive and severe diplopia, dysarthria, dysphagia, and facial weakness. Acetylcholine receptor antibodies and genetic testing for congenital myasthenic syndrome were negative. Muscle specific tyrosine kinase antibodies were significantly elevated. Ophthalmoplegia and bulbar weakness were refractory to treatment with acetylcholinesterase inhibitors, corticosteroids and IVIg but completely resolved following treatment with rituximab. Her neurologic examination remained normal at the most recent follow-up, 15 months after initiation of rituximab. Children with MuSK myasthenia, like adults, can respond to rituximab despite long standing disease and failure to improve on other immunosuppressant medications. PMID:25998611

  19. Myasthenia gravis associated with thymoma and toxic multinodular goiter. A case report.

    PubMed

    lonescu, Lidia; Stefănescu, Cipriana; Dănilă, R; Trifescu, Irina; Savin, M; Dragomir, C; Ferariu, D; Vulpoi, Carmen

    2012-01-01

    Adequate antithyroid drug treatment or surgery usually generates remission of myasthenia gravis (MG) in patients with thymus hyperplasia associated with Graves' hyperthyroidism. The case of a 46-year-old woman diagnosed with MG based on the clinical picture, anticholinesterase drug test and positive electromyography (EMG) is presented. The cervico-thoracic computer tomography revealed a compressive nodular goiter and normal antero-superior mediastinum and led to the diagnosis of MG secondary to the hyperthyroidism. An uneventful total thyroidectomy was performed, but postoperatively the MG symptoms worsened. TC99m tetrofosmin scintigraphy revealed an area of hyperfixation in the antero-inferior mediastinum, suggestive for thymoma, as confirmed by a repeated thoracic CT scan. Following a longitudinal sternotomy, a well incapsulated tumor of approximately 6/5 cm located in the antero-inferior mediastinum was found and an extensive thymomectomy was performed. The postoperative course was uneventful and the patient was discharged 9 days later with complete remission of myasthenia. The pathology report of the specimen revealed a mixt thymoma or AB thymoma after Muller-Hermelink and WHO classification, with invasive capsular foci corresponding to Masaoka II stadium. In conclusion, scintigraphy proved to be useful in the diagnosis and decision making of a thymoma. PMID:23077950

  20. Acute Respiratory Failure Induced by Magnesium Replacement in a 62-Year-Old Woman with Myasthenia Gravis

    PubMed Central

    Singh, Paramveer; Idowu, Olakunle; Malik, Imrana

    2015-01-01

    Magnesium is known to act at the neuromuscular junction by inhibiting the presynaptic release of acetylcholine and desensitizing the postsynaptic membrane. Because of these effects, magnesium has been postulated to potentiate neuromuscular weakness. We describe the case of a 62-year-old woman with myasthenia gravis and a metastatic thymoma who was admitted to our intensive care unit for management of a myasthenic crisis. The patient's neuromuscular weakness worsened in association with standard intravenous magnesium replacement, and the exacerbated respiratory failure necessitated intubation, mechanical ventilation, and an extended stay in the intensive care unit. The effect of magnesium replacement on myasthenia gravis patients has not been well documented, and we present this case to increase awareness and stimulate research. In addition, we discuss the relevant medical literature. PMID:26504451

  1. T-lymphocyte-rich Thymoma and Myasthenia Gravis in a Siberian Tiger (Panthera tigris altaica)☆

    PubMed Central

    Allan, K.; Masters, N.; Rivers, S.; Berry, K.; Routh, A.; Lamm, C.

    2014-01-01

    Summary A 10-year-old captive male Siberian tiger (Panthera tigris altaica) presented with acute onset collapse, vomiting and dyspnoea, preceded by a 6-month period of progressive muscle wasting. Following humane destruction, post-mortem examination revealed a large multilobulated mass in the cranial mediastinum, which was diagnosed as a T-lymphocyte-rich thymoma with the aid of immunohistochemistry. Retrospective serology for acetylcholine receptor antibodies (titre 3.90 nmol/l) confirmed a diagnosis of thymoma-associated myasthenia gravis. Thymomas are reported rarely in wild carnivores, but when detected they appear to be similar in morphology to those seen in domestic carnivores and may also be accompanied by paraneoplastic syndromes. The clinical signs of myasthenia gravis in the tiger were consistent with those reported in cats and dogs and the condition is proposed as an important differential diagnosis for generalized weakness in captive Felidae. PMID:24444818

  2. Acute Respiratory Failure Induced by Magnesium Replacement in a 62-Year-Old Woman with Myasthenia Gravis.

    PubMed

    Singh, Paramveer; Idowu, Olakunle; Malik, Imrana; Nates, Joseph L

    2015-10-01

    Magnesium is known to act at the neuromuscular junction by inhibiting the presynaptic release of acetylcholine and desensitizing the postsynaptic membrane. Because of these effects, magnesium has been postulated to potentiate neuromuscular weakness. We describe the case of a 62-year-old woman with myasthenia gravis and a metastatic thymoma who was admitted to our intensive care unit for management of a myasthenic crisis. The patient's neuromuscular weakness worsened in association with standard intravenous magnesium replacement, and the exacerbated respiratory failure necessitated intubation, mechanical ventilation, and an extended stay in the intensive care unit. The effect of magnesium replacement on myasthenia gravis patients has not been well documented, and we present this case to increase awareness and stimulate research. In addition, we discuss the relevant medical literature. PMID:26504451

  3. Factors that determine the severity of experimental myasthenia gravis.

    PubMed

    Drachman, D B; McIntosh, K R; Yang, B

    1998-05-13

    R antibody production than T cells with specificity for other Torpedo AChR epitopes. This results in production of greater amounts of AChR antibodies, including a critical subset that cross-reacts with autologous mouse AChR. The higher autoantibody levels contribute to the greater susceptibility to EAMG and to the greater severity of manifestations in the B6 strain compared with the bm12 strain. (4) There is a bias in B6 mice toward the production of AChR antibodies of IgG2b isotype. We suggest that T cells specific for alpha 146-162 may contribute to this isotype bias. The IgG2b antibodies appear to have particularly potent "myasthenogenic" effects in rats and mice. (5) Finally, it should be emphasized that these differences in immunological and clinical aspects of EAMG in B6 and bm12 mice are relative rather than absolute. T cells that respond to AChR epitopes other than alpha 146-162 can also provide help for AChR antibody production, albeit less potent. In a sense, this model represents a special case of molecular mimicry. In this case, the source of the foreign antigenic molecule is injection rather than the more usual route of infection. The antigen (Torpedo AChR) is one that these mice would never naturally encounter, and the critical amino acid (lysine 155) of the key epitope (alpha 146-162) is present only in the AChR of electric organs of electric fish and not in the AChR of mice, chickens, cows, or humans. The important point is that a detail of the structure of the foreign antigen--that is, a particular peptide of Torpedo AChR--can determine the severity of an antibody-mediated autoimmune disease, depending on how it interacts with a detail of the structure of the MHC Class II molecule and, in turn, on how the peptide/MHC Class II complex interacts with the available T cell repertoire. (ABSTRACT TRUNCATED) PMID:9668247

  4. Myasthenia Gravis

    MedlinePlus

    ... due to weakness of the muscles that control eye movements, unstable or waddling gait, a change in facial ... neurological examinations. The physician looks for impairment of eye movements or muscle weakness without any changes in the ...

  5. Myasthenia Gravis

    MedlinePlus

    ... symptoms are trouble with eye and eyelid movement, facial expression and swallowing. But it can also affect other muscles. The weakness gets worse with activity, and better with rest. There are medicines to ...

  6. Myasthenia gravis

    MedlinePlus

    ... breathing assistance with a ventilator . A procedure called plasmapheresis may also be used to help end the ... is free of antibodies, or with other fluids. Plasmapheresis may also help reduce symptoms for 4 to ...

  7. Myasthenia gravis

    MedlinePlus

    ... symptoms and other medicines have not worked well. Crisis situations are attacks of weakness of the breathing ... may also be used to help end the crisis. This procedure involves removing the clear part of ...

  8. Comparative effects of plasma exchange and pyridostigmine on respiratory muscle strength and breathing pattern in patients with myasthenia gravis.

    PubMed Central

    Goti, P.; Spinelli, A.; Marconi, G.; Duranti, R.; Gigliotti, F.; Pizzi, A.; Scano, G.

    1995-01-01

    BACKGROUND--Pyridostigmine, an acetylcholinesterase antagonist, is useful in improving respiratory function in patients with myasthenia gravis. More recently, plasma exchange has been employed in myasthenia gravis because it acts presumably by removal of circulating antibodies against acetylcholine receptors. Surprisingly, comparative data on the effects of pyridostigmine and plasma exchange on lung volumes, respiratory muscle strength, and ventilatory control system in patients with myasthenia gravis are lacking. METHODS--Nine consecutive patients with grade IIb myasthenia gravis were studied under control conditions and after a therapeutic dose of pyridostigmine. In a second study the patients were re-evaluated a few days after a cycle of plasma exchange, before taking pyridostigmine. In each subject pulmonary volumes, inspiratory (MIP) and expiratory (MEP) muscle force, and respiratory muscle strength, calculated as average MIP and MEP as percentages of their predicted values, were measured. The ventilatory control system was evaluated in terms of volume (tidal volume, VT) and time (inspiratory time, TI, and total time, TTOT) components of the respiratory cycle. Mean inspiratory flow (VT/TI)--that is, the "driving"--and TI/TTOT--that is, the "timing"--components of ventilation were also measured. RESULTS--In each patient treatment relieved weakness and tiredness, and dyspnoea grade was reduced with plasma exchange. Following treatment, vital capacity (VC) increased on average by 9.7% with pyridostigmine and by 14% with plasma exchange, and MIP increased by 18% and 26%, respectively. In addition, with plasma exchange but not with pyridostigmine forced expiratory volume in one second (FEV1) increased by 16% and MEP increased by 24.5%, while functional residual capacity (FRC) decreased a little (6.8%). The change in respiratory muscle strength was related to change in VC (r2 = 0.48). With plasma exchange, VT increased by 18.6% and VT/TI increased by 13.5%, while

  9. [A case of myasthenia gravis with invasive thymoma associated with diffuse panbronchiolitis, alopecia, dysgeusia, cholangitis and myositis].

    PubMed

    Maekawa, Risa; Shibuya, Hideki; Hideyama, Takuto; Shiio, Yasushi

    2014-01-01

    A 43-year-old man was admitted to our hospital because of diplopia, ptosis, and dysphagia that had begun three years previously. He was diagnosed with myasthenia gravis (MG) and invasive thymoma and treated with corticosteroid, thymectomy, and radiation therapy. Ten years after the thymectomy, computed tomography (CT) showed metastasis of the thymoma in the left lower lobe of the lung. Two years after this recurrence, when the patient was 55, respiratory symptoms such as wheezing, persistent cough, and dyspnea appeared. Chronic sinusitis, diffuse centrilobular opacities on CT, and positivity for HLA-B54 led to a diagnosis of diffuse panbronchiolitis (DPB). Despite treatment with clarithromycin, the respiratory symptoms worsened. The patient developed alopecia and body hair loss at the age of 56 followed by dysgeusia, cholangitis, and myositis with positivity for anti-Kv1.4 antibodies. Although treatment with an increased dose of corticosteroid improved hair loss, dysgeusia, cholangitis, and myositis, he died of progression of DPB and serious respiratory infection at the age of 58. In this case, various autoimmune disorders occurred together with MG as complications of thymoma. Although alopecia, dysgeusia, and myositis are already known as complications of MG associated with thymoma, cholangitis is not well-recognized since there have been few reports suggesting a causal relationship between cholangitis and thymoma. Furthermore, DPB caused by immunodeficiency and respiratory tract hypersensitivity associated with thymoma and HLA-B54, respectively, is the distinctive feature of our case. Neurologists should be aware that various organs can be damaged directly and indirectly by abnormal T cells from thymoma in patients with MG. PMID:25283823

  10. Direct Proof of the In Vivo Pathogenic Role of the AChR Autoantibodies from Myasthenia Gravis Patients

    PubMed Central

    Kordas, Gregory; Lagoumintzis, George; Sideris, Sotirios; Poulas, Konstantinos; Tzartos, Socrates J.

    2014-01-01

    Several studies have suggested that the autoantibodies (autoAbs) against muscle acetylcholine receptor (AChR) of myasthenia gravis (MG) patients are the main pathogenic factor in MG; however, this belief has not yet been confirmed with direct observations. Although animals immunized with AChR or injected with anti-AChR monoclonal Abs, or with crude human MG Ig fractions exhibit MG symptoms, the pathogenic role of isolated anti-AChR autoAbs, and, more importantly, the absence of pathogenic factor(s) in the autoAb-depleted MG sera has not yet been shown by in vivo studies. Using recombinant extracellular domains of the human AChR α and β subunits, we have isolated autoAbs from the sera of four MG patients. The ability of these isolated anti-subunit Abs and of the Ab-depleted sera to passively transfer experimental autoimmune MG in Lewis rats was investigated. We found that the isolated anti-subunit Abs were at least as efficient as the corresponding whole sera or whole Ig in causing experimental MG. Abs to both α- and β-subunit were pathogenic although the anti-α-subunit were much more efficient than the anti-β-subunit ones. Interestingly, the autoAb-depleted sera were free of pathogenic activity. The later suggests that the myasthenogenic potency of the studied anti-AChR MG sera is totally due to their anti-AChR autoAbs, and therefore selective elimination of the anti-AChR autoAbs from MG patients may be an efficient therapy for MG. PMID:25259739

  11. Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population

    PubMed Central

    Maniaol, Angelina H.; Elsais, Ahmed; Lorentzen, Åslaug R.; Owe, Jone F.; Viken, Marte K.; Sæther, Hanne; Flåm, Siri T.; Bråthen, Geir; Kampman, Margitta T.; Midgard, Rune; Christensen, Marte; Rognerud, Anna; Kerty, Emilia; Gilhus, Nils Erik; Tallaksen, Chantal M. E.

    2012-01-01

    Background Acquired myasthenia gravis (MG) is a rare antibody-mediated autoimmune disease caused by impaired neuromuscular transmission, leading to abnormal muscle fatigability. The aetiology is complex, including genetic risk factors of the human leukocyte antigen (HLA) complex and unknown environmental factors. Although associations between the HLA complex and MG are well established, not all involved components of the HLA predisposition to this heterogeneous disease have been revealed. Well-powered and comprehensive HLA analyses of subgroups in MG are warranted, especially in late onset MG. Methodology/Principal Findings This case-control association study is of a large population-based Norwegian cohort of 369 MG patients and 651 healthy controls. We performed comprehensive genotyping of four classical HLA loci (HLA-A, -B, -C and -DRB1) and showed that the DRB1*15:01 allele conferred the strongest risk in late onset MG (LOMG; onset ≥60years) (OR 2.38, pc7.4×10−5). DRB1*13:01 was found to be a protective allele for both early onset MG (EOMG) and LOMG (OR 0.31, pc 4.71×10−4), a finding not previously described. No significant association was found to the DRB1*07:01 allele (pnc = 0.18) in a subset of nonthymomatous anti-titin antibody positive LOMG as reported by others. HLA-B*08 was mapped to give the strongest contribution to EOMG, supporting previous studies. Conclusion The results from this study provide important new information concerning the susceptibility of HLA alleles in Caucasian MG, with highlights on DRB1*15:01 as being a major risk allele in LOMG. PMID:22590574

  12. Regulation of acetylcholine receptor alpha subunit variants in human myasthenia gravis. Quantification of steady-state levels of messenger RNA in muscle biopsy using the polymerase chain reaction.

    PubMed Central

    Guyon, T; Levasseur, P; Truffault, F; Cottin, C; Gaud, C; Berrih-Aknin, S

    1994-01-01

    Myasthenia gravis (MG) is an autoimmune disease mediated by auto-antibodies that attack the nicotinic acetylcholine receptor (AChR). To elucidate the molecular mechanisms underlying the decrease in AChR levels at the neuromuscular junction, we investigated the regulation of AChR expression by analyzing mRNA of the two AChR alpha subunit isoforms (P3A+ and P3A-) in muscle samples from myasthenic patients relative to controls. We applied a quantitative method based on reverse transcription of total RNA followed by polymerase chain reaction (PCR), using an internal standard we constructed by site-directed mutagenesis. An increased expression of mRNA coding for the alpha subunit of the AChR isoforms was observed in severely affected patients (P < 0.003 versus controls) but not in moderately affected patients, independently of the anti-AChR antibody titer. Study of mRNA precursor levels indicates a higher expression in severely affected patients compared to controls, suggesting an enhanced rate of transcription of the message coding for the alpha subunit isoforms in these patients. We have also reported that mRNA encoding both isoforms are expressed at an approximate 1:1 ratio in controls and in patients. We have thus identified a new biological parameter correlated with disease severity, and provide evidence of a compensatory mechanism to balance the loss of AChR in human myasthenia gravis, which is probably triggered only above a certain degree of AChR loss. Images PMID:8040257

  13. Ocular myasthenia gravis: treatment successes and failures in patients with long-term follow-up.

    PubMed

    Kupersmith, Mark J

    2009-08-01

    We previously reported that prednisone reduced the frequency of generalized myasthenia (GMG) and controlled diplopia without major adverse effects at 2 years in patients with ocular myasthenia gravis (OMG). Questions remain as to whether study subjects had long-standing disease, biasing results towards a steroid benefit, and if prednisone merely delayed GMG onset. Here, we performed a record review of a referral neuro-ophthalmology service OMG database for patients who were followed-up for > or =4 years or until GMG developed. We studied the effect of prednisone on GMG incidence and control of ocular symptoms. Generally, patients with diplopia were recommended for prednisone therapy. Most remained on daily 2.5-10 mg for diplopia control. We compared the results for prednisone-treated and "untreated" (pyridostigmine only) patients. Of 87 patients, 55 were in the prednisone-treated and 32 were in the untreated groups. GMG developed in 7 (13%) of the prednisone-treated (OR 0.41; 95% CI 0.22-0.76) and in 16 (50%) of the untreated (OR 2.78; 95% CI 1.68-4.60) patients. After OMG onset, GMG developed at a mean 5.8 and 0.22 years in prednisone and untreated groups. Diplopia was present at the last exam in 27% of the prednisone-treated (mean 7.2 years) and in 57% of the untreated (mean 4.6 years) OMG patients. For 48 prednisone-treated patients who did not develop GMG, OMG treatment failure occurred in 13. Thus, prednisone delays the onset of GMG and has sustained benefit in reducing the incidence of GMG and controlling diplopia. Without prednisone, GMG develops in 50% of OMG patients, typically within 1 year. PMID:19377863

  14. Comparison of outcomes after extended thymectomy for myasthenia gravis: bilateral thoracoscopic approach versus sternotomy.

    PubMed

    Shiono, Hiroyuki; Kadota, Yoshihisa; Hayashi, Akio; Okumura, Meinoshin

    2009-12-01

    Minimally invasive thymectomy procedures have been proposed for nonthymomatous myasthenia gravis. However, few reports stressed that the lower invasiveness or cosmetic benefits also evaluated the rationale of a thymectomy, which is performed to remove as much thymic tissue as possible. We retrospectively reviewed 30 consecutive patients who underwent a bilateral video-assisted thoracoscopic extended thymectomy (VATET) and compared the results with those of 26 patients who underwent a transsternal extended thymectomy (TSET) to determine the amount of removed thymic tissue and clinical prognosis. The amount of blood loss during the operation for VATET (median 60 mL; range nearly 0 to 940 mL) was significantly lower as compared with that of TSET. The median weight of removed thymic tissue (37.0 g; 18.3 to 100.0 g) and remission rates (1 y: 12.5%; 3 y: 30.8%; 4 y: 44.4%) of VATET were comparable with those of TSET. The VATET group had a similar amount of thymo-fatty tissue removed and feasible clinical outcomes as compared with the TSET group, indicating that VATET provides a proper balance between less invasiveness and radical capability. PMID:20027081

  15. Genetic heterogeneity within the HLA region in three distinct clinical subgroups of myasthenia gravis.

    PubMed

    Saruhan-Direskeneli, Güher; Hughes, Travis; Yilmaz, Vuslat; Durmus, Hacer; Adler, Adam; Alahgholi-Hajibehzad, Mahdi; Aysal, Fikret; Yentür, Sibel P; Akalin, Mehmet Ali; Dogan, Oner; Marx, Alexander; Gülsen-Parman, Yesim; Oflazer, Piraye; Deymeer, Feza; Sawalha, Amr H

    2016-05-01

    This study aims to investigate genetic susceptibility to early-onset and late-onset anti-acetylcholine receptor antibody positive myasthenia gravis (EOMG and LOMG) and anti-muscle specific kinase antibody positive MG (MuSK-MG) at genome-wide level in a single population. Using a custom-designed array and imputing additional variants and the classical HLA alleles in 398 patients, we detected distinct associations. In EOMG, rs113519545 in the HLA class I region (OR=5.71 [3.77-8.66], P=2.24×10(-16)), HLA-B*08:01 (OR=7.04 [3.95-12.52], P=3.34×10(-11)) and HLA-C*07:01 (OR=2.74 [1.97-3.81], P=2.07(-9)), in LOMG, rs111256513 in the HLA class II region (OR=2.22 [1.59-3.09], P=2.48×10(-6)) and in MuSK-MG, an intronic variant within HLA-DQB1 (rs68081734, OR=5.86, P=2.25×10(-14)) and HLA-DQB1*05:02 (OR=8.56, P=6.88×10(-13)) revealed the most significant associations for genome-wide significance. Differential genetic susceptibility within the HLA to EOMG, LOMG and MuSK-MG has been established in a population from Turkey. PMID:27181991

  16. Myasthenia gravis with muscle specific kinase antibodies mimicking amyotrophic lateral sclerosis.

    PubMed

    Huijbers, Maartje G; Niks, Erik H; Klooster, Rinse; de Visser, Marianne; Kuks, Jan B; Veldink, Jan H; Klarenbeek, Pim; Van Damme, Philip; de Baets, Marc H; van der Maarel, Silvère M; van den Berg, Leonard H; Verschuuren, Jan J

    2016-06-01

    Muscle-specific kinase (MuSK) myasthenia gravis (MG) is hallmarked by the predominant involvement of bulbar muscles and muscle atrophy. This might mimic amyotrophic lateral sclerosis (ALS) presenting with bulbar weakness. We encountered four cases of MuSK MG patients with an initial misdiagnosis of ALS. We analyzed the clinical data of the four misdiagnosed MuSK MG patients, and investigated the presence of MuSK autoantibodies in a group of 256 Dutch bulbar-onset ALS patients using a recombinant MuSK ELISA and a standard MuSK radioimmunorecipitation assay. Clues for changing the diagnosis were slow progression, clinical improvement, development of diplopia and absence of signs of upper motor neuron involvement. No cases of MuSK MG were identified among a group of 256 bulbar ALS patients diagnosed according to the revised El Escorial criteria. A misdiagnosis of ALS in patients with MuSK MG is rare. We recommend to carefully consider the diagnosis of MuSK MG in patients presenting with bulbar weakness without clear signs of upper motor neuron dysfunction. PMID:27133662

  17. [Intractable Myasthenia Gravis Accompanied with Thymoma;Report of a Case].

    PubMed

    Naomi, Akira; Oyamatsu, Yoshinori; Narita, Kunio; Nakayama, Masato; Maeda, Shoki

    2016-09-01

    A 46-year-old female visited a hospital due to pelvic inflammatory disease (PID) and then her chest computed tomography revealed an abnormal shadow in the upper mediastinum. Four months later,she complained muscle weakness with her limbs, dysphagia, and ptosis of her eyelids. Total thymectomy was performed through a median sternotomy for mass lesion, which was pathologically proven to be type B1 thymoma. Postoperative myasthenia gravis (MG) crisis, which led to respiratory failure requiring intubation and mechanical ventilation, developed and laboratory tests showed elevated serum anti-AChR Ab(130 nmol/l), antinuclear antibody( ×640 serum dilution, speckled pattern) and anti-RNP Ab(129.2 U/ml). For MG crisis, steroid pulse therapy, immunosuppressive therapy and immuno absorption were performed, and she successfully weaned from mechanical ventilaton on 41 post operative day (POD). Some factors such as inapparent mixed connective tissue disease (MCTD) and Anti RNP antibody were thought to be a cause for having any difficulty in MG treatment in the present case. PMID:27586323

  18. Diagnosis of Ocular Myasthenia Gravis by means of tracking eye parameters.

    PubMed

    Azri, Muhammad; Young, Stephanie; Lin, Hazel; Tan, Clement; Yang, Zhi

    2014-01-01

    Ptosis of the eyelids is a common condition with a myriad of causes. Its management depends on the underlying cause, which can be challenging to diagnose in some cases. Current diagnosis methods include serum antibodies, tensilon test, and electromyography (EMG). Each has its own set of limitations such as invasiveness and lack of sensitivity. To overcome these limitations, we have developed a Portable Realtime Infrared Lids, Iris and Blink (PRILIB) monitoring system, with a long-term goal to improve clinical diagnosis of ptosis. In this paper, we present the algorithms to detect and analyze eye parameters and report experimental results. From experiments conducted on normal volunteers and myasthenic patients, we found 1. Partial blinks happen when Ocular Myasthenia Gravis (OMG) patients are tired or engaged in an activity; 2. Blink rate is significantly higher for OMG patients due to failure to blink fully; 3. There are noticeably more fluctuations of palpebral aperture of OMG patients due to rising and falling of the eyelid height. These experimental findings suggest new diagnostic features for OMG patients and have implications for disease management. PMID:25570244

  19. Thymectomy for myasthenia gravis: outcome of treatment in a tertiary hospital.

    PubMed

    Torres, M I; Danguilan, J L

    1998-08-01

    The clinical records of 24 of the 31 patients who underwent thymectomy for myasthenia gravis from January 1991 to December 1995 were reviewed. The mean age of patients was 36.5 years, with a male : female ratio of 1 : 5. The average duration of symptoms prior to consultation was 16.6 months. Most of the patients presented diplopia with clinical stage IIA prior to surgery. The most common procedure utilized was thymectomy via a median sternotomy under general anesthesia-epidural anesthesia. Five of the 24 patients (21%) were immediately extubated postoperatively while 19 remained intubated, with 12 patients attached to a ventilator. Extubation ranged from the first postoperative day up to more than two weeks postoperatively. The average length of ICU stay was 8.1 days and the average length of hospital stay was 31.1 days. The most common morbidity was pneumonia (38%). One patient had a brief reactive psychosis and another patient had phrenic nerve injury which manifested 2 weeks postoperatively. The average length of follow-up was 14.8 months and the mean follow-up period was 24.5 months. There was a general trend of decrease in the dose of medication. However, there was an increase in the medication in 3 patients with 2 showing clinical improvement. PMID:9738120

  20. Antibodies against low-density lipoprotein receptor-related protein 4 induce myasthenia gravis.

    PubMed

    Shen, Chengyong; Lu, Yisheng; Zhang, Bin; Figueiredo, Dwight; Bean, Jonathan; Jung, Jiung; Wu, Haitao; Barik, Arnab; Yin, Dong-Min; Xiong, Wen-Cheng; Mei, Lin

    2013-12-01

    Myasthenia gravis (MG) is the most common disorder affecting the neuromuscular junction (NMJ). MG is frequently caused by autoantibodies against acetylcholine receptor (AChR) and a kinase critical for NMJ formation, MuSK; however, a proportion of MG patients are double-negative for anti-AChR and anti-MuSK antibodies. Recent studies in these subjects have identified autoantibodies against low-density lipoprotein receptor-related protein 4 (LRP4), an agrin receptor also critical for NMJ formation. LRP4 autoantibodies have not previously been implicated in MG pathogenesis. Here we demonstrate that mice immunized with the extracellular domain of LRP4 generated anti-LRP4 antibodies and exhibited MG-associated symptoms, including muscle weakness, reduced compound muscle action potentials (CMAPs), and compromised neuromuscular transmission. Additionally, fragmented and distorted NMJs were evident at both the light microscopic and electron microscopic levels. We found that anti-LRP4 sera decreased cell surface LRP4 levels, inhibited agrin-induced MuSK activation and AChR clustering, and activated complements, revealing potential pathophysiological mechanisms. To further confirm the pathogenicity of LRP4 antibodies, we transferred IgGs purified from LRP4-immunized rabbits into naive mice and found that they exhibited MG-like symptoms, including reduced CMAP and impaired neuromuscular transmission. Together, these data demonstrate that LRP4 autoantibodies induce MG and that LRP4 contributes to NMJ maintenance in adulthood. PMID:24200689

  1. Antibodies against low-density lipoprotein receptor–related protein 4 induce myasthenia gravis

    PubMed Central

    Shen, Chengyong; Lu, Yisheng; Zhang, Bin; Figueiredo, Dwight; Bean, Jonathan; Jung, Jiung; Wu, Haitao; Barik, Arnab; Yin, Dong-Min; Xiong, Wen-Cheng; Mei, Lin

    2013-01-01

    Myasthenia gravis (MG) is the most common disorder affecting the neuromuscular junction (NMJ). MG is frequently caused by autoantibodies against acetylcholine receptor (AChR) and a kinase critical for NMJ formation, MuSK; however, a proportion of MG patients are double-negative for anti-AChR and anti-MuSK antibodies. Recent studies in these subjects have identified autoantibodies against low-density lipoprotein receptor–related protein 4 (LRP4), an agrin receptor also critical for NMJ formation. LRP4 autoantibodies have not previously been implicated in MG pathogenesis. Here we demonstrate that mice immunized with the extracellular domain of LRP4 generated anti-LRP4 antibodies and exhibited MG-associated symptoms, including muscle weakness, reduced compound muscle action potentials (CMAPs), and compromised neuromuscular transmission. Additionally, fragmented and distorted NMJs were evident at both the light microscopic and electron microscopic levels. We found that anti-LRP4 sera decreased cell surface LRP4 levels, inhibited agrin-induced MuSK activation and AChR clustering, and activated complements, revealing potential pathophysiological mechanisms. To further confirm the pathogenicity of LRP4 antibodies, we transferred IgGs purified from LRP4-immunized rabbits into naive mice and found that they exhibited MG-like symptoms, including reduced CMAP and impaired neuromuscular transmission. Together, these data demonstrate that LRP4 autoantibodies induce MG and that LRP4 contributes to NMJ maintenance in adulthood. PMID:24200689

  2. Phenotypic and functional characterization of T cells from patients with myasthenia gravis.

    PubMed Central

    Mokhtarian, F; Pino, M; Ofosu-Appiah, W; Grob, D

    1990-01-01

    A study of cell surface phenotypes of PBL of myasthenia gravis (MG) patients showed that their T cells had a significantly higher percentage of 4B4+ T cells (the helper/inducer subset) than age- and sex-matched controls. The PBL of MG patients proliferated significantly higher than those of normal subjects (NS) in response to the purified alpha chain of the acetylcholine receptor (AChR). Anti-AChR antibody was present in sera of 88% of MG and none of the NS. The PBL B cells from MG only, when cultured with autologous T cells and stimulated with either pokeweed mitogen (69%), or AChR-alpha chain (38%), secreted antibody to AChR-alpha chain, whereas T and B cells alone secreted no antibody. T cells from PBL of MG patients were more readily cloned than T cells of NS, by limiting dilution, in the presence of recombinant IL-2 and in the absence of AChR-alpha chain. About 50% of T cell clones from MG patients, compared to none from NS, proliferated to AChR-alpha chain. This response was HLA-DR restricted. MG T cell clones did not display significant cytotoxic activity, as compared to control T cell clones. Our results indicate that in MG, 4B4+ regulatory T cells play their role in the pathogenesis of MG, not by cytotoxicity, but more likely by their ability to stimulate specific antibody production by B cells. Images PMID:1979338

  3. A reliability study of impairment and disability scales for myasthenia gravis patients.

    PubMed

    Romani, Alfredo; Piccolo, Giovanni; Bergamaschi, Roberto; Versino, Maurizio; Cosi, Vittorio

    2002-01-01

    The authors developed two scales to be adopted for the evaluation of myasthenia gravis (MG) patients. The first scale (MG impairment scale) is based on objective patient evaluation and on patients' responses to standardized questions relating to the functioning of specific muscle groups. It consists of 13 items exploring strength and 10 items exploring fatigability. The second scale (MG disability scale) evaluates disability in those everyday activities that are often impaired in MG patients. Test-retest reliability of each item and of the global score (sum of single item scores) was assessed by the weighted K statistic and by the intraclass correlation coefficient. Reliability was invariably 'substantial', and for single items 'almost perfect' for the MG impairment scale, and invariably 'almost perfect' for the MG disability scale. The internal structure of the MG impairment scale was explored by means of the principal component analysis. This analysis resulted in three main (rotated) factors, which loaded respectively onto 'ocular', 'spinal' and 'bulbar' functions. For these factors, we report factor score coefficients that can be used to compute single patients' scores, which in turn may be used in further analyses, particularly for follow-up studies. We also report the results of an analysis of the correlations between the two scales. The MG impairment and the MG disability scales are proposed for application in both clinical and research settings. PMID:12549719

  4. Specific binding of collagen Q to the neuromuscular junction is exploited to cure congenital myasthenia and to explore bases of myasthenia gravis.

    PubMed

    Ohno, Kinji; Ito, Mikako; Kawakami, Yu; Krejci, Eric; Engel, Andrew G

    2013-03-25

    Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ) in the form of asymmetric AChE (AChE/ColQ). The C-terminal domain of ColQ binds to MuSK, the muscle-specific receptor tyrosine kinase, that mediates a signal for acetylcholine receptor (AChR) clustering at the NMJ. ColQ also binds to heparan sulfate proteoglycans including perlecan. Congenital defects of ColQ cause endplate AChE deficiency. A single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq-/- mice rescued motor functions, synaptic transmission, and the ultrastructure of NMJ. We also injected AAV1-COLQ-IRES-EGFP to the left tibialis anterior and observed colocalization of AChE/ColQ at all the examined NMJs of the non-injected limbs. Additionally, injection of purified recombinant AChE/ColQ protein complex into gluteus maximus accumulated AChE in non-injected forelimbs. These observations suggest that the tissue-targeting signal of ColQ can be exploited to specifically deliver the transgene product to the target tissue. MuSK antibody-positive myasthenia gravis (MG) accounts for 5-15% of autoimmune MG. As AChR deficiency is typically mild and as cholinesterase inhibitors are generally ineffective or worsen myasthenic symptoms, we asked if the patient's MuSK-IgG interferes with binding of ColQ to MuSK. In vitro overlay of AChE/ColQ to muscle sections of Colq-/- mice revealed that MuSK-IgG blocks binding of ColQ to the NMJ. In vitro plate-binding of MuSK to ColQ disclosed that MuSK-IgG exerts a dose-dependent block of MuSK-ColQ interaction. In addition, passive transfer of MuSK-IgG to mice reduced the size and density of ColQ to ∼10% of controls and had a lesser effect on the sizes and densities of AChR and MuSK. Elucidation of molecular mechanisms of specific binding of ColQ to the NMJ enabled us to ameliorate devastating myasthenic symptoms of Colq-/- mice and to reveal bases of

  5. Specific binding of collagen Q to the neuromuscular junction is exploited to cure congenital myasthenia and to explore bases of myasthenia gravis

    PubMed Central

    Ohno, Kinji; Ito, Mikako; Kawakami, Yu; Krejci, Eric; Engel, Andrew G.

    2015-01-01

    Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ) in the form of asymmetric AChE (AChE/ColQ). The C-terminal domain of ColQ binds to MuSK, the muscle-specific receptor tyrosine kinase, that mediates a signal for acetylcholine receptor (AChR) clustering at the NMJ. ColQ also binds to heparan sulfate proteoglycans including perlecan. Congenital defects of ColQ cause endplate AChE deficiency. A single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq−/− mice rescued motor functions, synaptic transmission, and the ultrastructure of NMJ. We also injected AAV1-COLQ-IRES-EGFP to the left tibialis anterior and observed colocalization of AChE/ColQ at all the examined NMJs of the non-injected limbs. Additionally, injection of purified recombinant AChE/ColQ protein complex into gluteus maximus accumulated AChE in non-injected forelimbs. These observations suggest that the tissue-targeting signal of ColQ can be exploited to specifically deliver the transgene product to the target tissue. MuSK antibody-positive myasthenia gravis (MG) accounts for 5–15% of autoimmune MG. As AChR deficiency is typically mild and as cholinesterase inhibitors are generally ineffective or worsen myasthenic symptoms, we asked if the patient's MuSK-IgG interferes with binding of ColQ to MuSK. In vitro overlay of AChE/ColQ to muscle sections of Colq−/− mice revealed that MuSK-IgG blocks binding of ColQ to the NMJ. In vitro plate-binding of MuSK to ColQ disclosed that MuSK-IgG exerts a dose-dependent block of MuSK-ColQ interaction. In addition, passive transfer of MuSK-IgG to mice reduced the size and density of ColQ to ~10% of controls and had a lesser effect on the sizes and densities of AChR and MuSK. Elucidation of molecular mechanisms of specific binding of ColQ to the NMJ enabled us to ameliorate devastating myasthenic symptoms of Colq−/− mice and to reveal

  6. Therapeutic target of memory B cells depletion helps to tailor administration frequency of rituximab in myasthenia gravis.

    PubMed

    Lebrun, Christine; Bourg, Véronique; Bresch, Saskia; Cohen, Mikael; Rosenthal-Allieri, Maria Alessandra; Desnuelle, Claude; Ticchioni, Michel

    2016-09-15

    Rituximab (RTX) has demonstrated efficacy in limiting relapses in myasthenia gravis (MG). We investigated the interest of CD27+ memory B cell monitoring in patients as a biological marker of clinical relapse. Twenty-four patients have been treated with RTX (375mg/m(2)/week-month as an induction treatment). Maintenance treatment consisted with either systematic treatment every 3months or only when CD27+ memory B cells were detectable. After the induction treatment, the mean infusions were 1.3/year compared with 4/year. We suggest that RTX administration frequency can be decreased safely by monitoring the re-emerging CD27+ memory B cells. PMID:27609279

  7. Rituximab in refractory myasthenia gravis: a prospective, open-label study with long-term follow-up.

    PubMed

    Anderson, Dustin; Phan, Cecile; Johnston, Wendy S; Siddiqi, Zaeem A

    2016-07-01

    We examined the clinical effectiveness of rituximab in fourteen patients with refractory myasthenia gravis (MG). Manual muscle testing (MMT) score was recorded at baseline and followed during the course of the study. Steroid dose, frequency of intravenous immunoglobulin (IVIG) infusions, and plasma exchange (PLEX) were also monitored throughout the duration of the study. All patients responded dramatically to rituximab, as measured by a change in MMT score, prednisone dose, or the frequency of IVIG infusions or PLEX. Rituximab appears safe and effective for the treatment of refractory MG. It should be considered as a therapeutic option in refractory patients. PMID:27386504

  8. The Association of PTPN22 R620W Polymorphism Is Stronger with Late-Onset AChR-Myasthenia Gravis in Turkey

    PubMed Central

    Kaya, Gizem A.; Coşkun, Ayse N.; Yılmaz, Vuslat; Oflazer, Piraye; Gülsen-Parman, Yeşim; Aysal, Fikret; Disci, Rian; Direskeneli, Haner; Marx, Alexander; Deymeer, Feza; Saruhan-Direskeneli, Güher

    2014-01-01

    A functional single nucleotide polymorphism (SNP) of the PTPN22 gene encoding a protein tyrosine phosphatase has been associated with autoimmune disorders including myasthenia gravis (MG). As the PTPN22 R620W polymorphism has a wide variation of allele frequencies among different populations, this polymorphism was investigated in MG in Turkey. An emphasis is put on MG subgroups according to autoantibody (Abs) production and presence of thymoma. DNA samples from 416 patients with clinically diagnosed generalized MG (231 with Abs to acetylcholine receptor, AChR-MG), 53 with Abs to muscle-specific kinase (MuSK-MG), 55 patients with no detectable Abs (SN-MG), 77 patients with thymoma (TAMG) and 293 healthy controls (HC) were genotyped for the SNP (PTPN22 R620W, C1858T, rs2476601). The PTPN22 T allele was increased in AChR-MG patients (odds ratio [OR]: 2.5, 95%CI: 1.2–5.1). The association was stronger in late disease-onset AChR (LOMG, OR: 3.1, 95%CI: 1.2–8.2). MuSK-MG, SN-MG and TAMG groups did not carry the variant allele more frequently than the HC. In contrast to findings in other autoimmune diseases, the distribution of the PTPN22 polymorphism in this population provides a susceptibility marker for AChR-MG. The strongest association is detected in patients with LOMG. PMID:25119822

  9. Blockade of CD40 ligand suppresses chronic experimental myasthenia gravis by down-regulation of Th1 differentiation and up-regulation of CTLA-4.

    PubMed

    Im, S H; Barchan, D; Maiti, P K; Fuchs, S; Souroujon, M C

    2001-06-01

    Myasthenia gravis (MG) and experimental autoimmune MG (EAMG) are T cell-dependent Ab-mediated autoimmune disorders, in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. Th1-type cells and costimulatory factors such as CD40 ligand (CD40L) contribute to disease pathogenesis by producing proinflammatory cytokines and by activating autoreactive B cells. In this study we demonstrate the capacity of CD40L blockade to modulate EAMG, and analyze the mechanism underlying this disease suppression. Anti-CD40L Abs given to rats at the chronic stage of EAMG suppress the clinical progression of the autoimmune process and lead to a decrease in the AChR-specific humoral response and delayed-type hypersensitivity. The cytokine profile of treated rats suggests that the underlying mechanism involves down-regulation of AChR-specific Th1-regulated responses with no significant effect on Th2- and Th3-regulated AChR-specific responses. EAMG suppression is also accompanied by a significant up-regulation of CTLA-4, whereas a series of costimulatory factors remain unchanged. Adoptive transfer of splenocytes from anti-CD40L-treated rats does not protect recipient rats against subsequently induced EAMG. Thus it seems that the suppressed progression of chronic EAMG by anti-CD40L treatment does not induce a switch from Th1 to Th2/Th3 regulation of the AChR-specific immune response and does not induce generation of regulatory cells. The ability of anti-CD40L treatment to suppress ongoing chronic EAMG suggests that blockade of CD40L may serve as a potential approach for the immunotherapy of MG and other Ab-mediated autoimmune diseases. PMID:11359850

  10. Evaluation of the Quality of Guidelines for Myasthenia Gravis with the AGREE II Instrument

    PubMed Central

    Zhang, Zhenchang; Guo, Jia; Su, Gang; Li, Jiong; Wu, Hua; Xie, Xiaodong

    2014-01-01

    Background Clinical practice guidelines (CPGs) are systematically developed statements to assist practitioners in making decisions about appropriate healthcare in specific clinical circumstances. The methodological quality of CPGs for myasthenia gravis (MG) are unclear. Objective To critically evaluate the methodological quality of CPGs for MG using AGREE II instrument. Method A systematical search strategy on PubMed, EMBASE, DynaMed, the National Guideline Clearinghouse (NGC) and the Chinese Biomedical Literature database (CBM) was performed on September 20th 2013. All guidelines related to MG were evaluated with AGREE II. The software used for analysis was SPSS 17.0. Results A total of 15 CPGs for MG met the inclusion criteria (12 CPGs in English, 3 CPGs in Chinese). The overall agreement among reviews was moderate or high (ICC >0.70). The mean scores (mean ± SD) for al six domains were presented as follows: scope and purpose (60.93% ±16.62%), stakeholder involvement (40.93% ±20.04%), rigor of development (37.22% ±30.46%), clarity of presentation (64.26% ±16.36%), applicability (28.19% ±20.56%) and editorial independence (27.78% ±28.28%). Compared with non-evidence-based CPGs, evidence-based CPGs had statistically significant higher quality scores for all AGREE II domains (P<0.05). All domain scores appear slightly higher for CPGs published after AGREE II instrument development and validation (P>0.05). The quality scores of CPGs developed by NGC/AAN were higher than the quality scores of CPGs developed by other organizations for all domains. The difference was statistically significant for all domains with the exception of clarity of presentation (P = 0.07). Conclusions The qualities of CPGs on MG were generally acceptable with several flaws. The AGREE II instrument should be adopted by guideline developers, particularly in China. PMID:25402504

  11. Expression of acetylcholine receptor genes in human thymic epithelial cells: implications for myasthenia gravis.

    PubMed

    Wakkach, A; Guyon, T; Bruand, C; Tzartos, S; Cohen-Kaminsky, S; Berrih-Aknin, S

    1996-10-15

    The intrathymic presence of the muscle acetylcholine receptor (AChR) is controversial, and the nature of the cell(s) expressing it is unclear. We thus analyzed the molecular expression of muscle AChR in human thymi. mRNA studies indicated that the two isoforms (P3A+ and P3A-) of the alpha-subunit were present in thymic extracts and in cultured thymic epithelial cells (TEC), while expression in thymocytes was low and not consistently detectable. The amount of mRNA coding for the alpha-subunit, evaluated by means of quantitative PCR, was about 20 times less in TEC than in muscle, and was similar in TEC from normal subjects and from patients with myasthenia gravis (MG). The beta- and epsilon-subunits present in adult AChR were also expressed in TEC (but not in thymocytes), while the embryonic subunit (gamma) was absent. In TEC cultures, the AChR alpha- and epsilon-subunit mRNA levels were down-regulated by forskolin, as also observed in the TE671 rhabdomyosarcoma cell line, suggesting similar regulation of AChR subunits in thymus and muscle. Protein expression was evidenced on TEC (but not on thymocytes), by Western blotting as well as by immunofluorescence, thus demonstrating AChR expression on human thymic epithelial cells. There was no difference in the expression of AChR between TEC from MG patients and controls, meaning that the expression of AChR subunits alone is not sufficient to explain the onset of MG. PMID:8871679

  12. Validation of the MG-DIS: a disability assessment for myasthenia gravis.

    PubMed

    Raggi, Alberto; Leonardi, Matilde; Schiavolin, Silvia; Antozzi, Carlo; Brenna, Greta; Maggi, Lorenzo; Mantegazza, Renato

    2016-05-01

    This paper is aimed to present the validation of the myasthenia gravis disability assessment (MG-DIS), a MG-specific patient-reported disability outcome measure. Consecutive MG patients were enrolled, followed-up for 12 months and administered the SF-36, the WHO disability assessment schedule (WHODAS 2.0) and the preliminary 31-item MG-DIS addressing impairments and activity limitations. Factor structure and metric properties were assessed. In total, 109 patients were enrolled: 76 were females, mean age 50, mean MG duration 10.4 years, 86 were AChR-positive. The MG-DIS was reduced to 20 items, explaining 70.6 % of the original questionnaire variance, four subscales (generalized impairment-related problems; bulbar function-related problems; mental health and fatigue-related problems; vision-related problems) and an overall disability index. The MG-DIS has good metric properties (Cronbach's alpha ranging between .808 and .930), is stable, showed to be more sensitive than the WHODAS 2.0 and SF-36 to detect group differences and longitudinal changes and was well correlated with the MG-composite (.642). The MG-DIS includes items representing ocular, generalized, bulbar and respiratory symptoms, and is therefore well-built around MG-specific features. MG-DIS can be used in clinical trials as well as in observational or epidemiological studies to characterize patients' disability level and address the amount of improvement in disability. Further studies are needed to explore the possibility of a shorter disability scale. PMID:26931109

  13. Microenvironments in the normal thymus and the thymus in myasthenia gravis.

    PubMed Central

    Bofill, M.; Janossy, G.; Willcox, N.; Chilosi, M.; Trejdosiewicz, L. K.; Newsom-Davis, J.

    1985-01-01

    The disposition of epithelial cells and extracellular matrix, in the thymus of 8 cases of myasthenia gravis (MG) and in controls (over a wide age range) was studied. In the controls, the subcapsular epithelium was strongly Leu-7-positive in the fetus, negative in childhood, and positive again in adults. Another antibody, RFD4, also labeled the subcapsular epithelium in childhood and adults, but not fetal samples. The samples from MG cases showed the same staining pattern as adult control samples. The medullary epithelium was also RFD4+, and at all ages. The most striking changes in the advanced cases of MG were the unusual arrangement and hypertrophic appearance of medullary epithelial cell areas, separated by laminin-positive basement membranes from the alternating multiple bands of peripheral lymph-node-like areas. The latter had regions resembling the paracortex of lymph nodes as well as germinal centers (GCs). The T-cell zones contained heavy deposits of fibronectin. These T-cell zones were unique to the thymus in MG and were absent in the two normal thymic samples with isolated GCs. In MG the laminin-containing basement membrane, which separated the medullary epithelial and peripheral lymph-node-like areas, was fenestrated at circumscribed points closest to the GCs, thus apparently permitting communication among the medullary epithelium, the T-cell zones, the GCs and the associated antigen-presenting cells. Large numbers of interdigitating cells and some lymphocytes of cortical thymocyte phenotype were also found at these special sites, where opportunities for autosensitization may persist in MG. Images Figure 7 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3874554

  14. Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis.

    PubMed

    Phillips, W D; Christadoss, P; Losen, M; Punga, A R; Shigemoto, K; Verschuuren, J; Vincent, A

    2015-08-01

    Muscle-specific tyrosine kinase (MuSK) autoantibodies are the hallmark of a form of myasthenia gravis (MG) that can challenge the neurologist and the experimentalist. The clinical disease can be difficult to treat effectively. MuSK autoantibodies affect the neuromuscular junction in several ways. When added to muscle cells in culture, MuSK antibodies disperse acetylcholine receptor clusters. Experimental animals actively immunized with MuSK develop MuSK autoantibodies and muscle weakness. Weakness is associated with reduced postsynaptic acetylcholine receptor numbers, reduced amplitudes of miniature endplate potentials and endplate potentials, and failure of neuromuscular transmission. Similar impairments have been found in mice injected with IgG from MG patients positive for MuSK autoantibody (MuSK-MG). The active and passive models have begun to reveal the mechanisms by which MuSK antibodies disrupt synaptic function at the neuromuscular junction, and should be valuable in developing therapies for MuSK-MG. However, translation into new and improved treatments for patients requires procedures that are not too cumbersome but suitable for examining different aspects of MuSK function and the effects of potential therapies. Study design, conduct and analysis should be carefully considered and transparently reported. Here we review what has been learnt from animal and culture models of MuSK-MG, and offer guidelines for experimental design and conduct of studies, including sample size determination, randomization, outcome parameters and precautions for objective data analysis. These principles may also be relevant to the increasing number of other antibody-mediated diseases that are now recognized. PMID:25542979

  15. VAV1 and BAFF, via NFκB pathway, are genetic risk factors for myasthenia gravis

    PubMed Central

    Avidan, Nili; Le Panse, Rozen; Harbo, Hanne F; Bernasconi, Pia; Poulas, Konstantinos; Ginzburg, Elizabeta; Cavalcante, Paola; Colleoni, Lara; Baggi, Fulvio; Antozzi, Carlo; Truffault, Frédérique; Horn-Saban, Shirley; Pöschel, Simone; Zagoriti, Zoi; Maniaol, Angelina; Lie, Benedicte A; Bernard, Isabelle; Saoudi, Abdelhadi; Illes, Zsolt; Casasnovas Pons, Carlos; Melms, Arthur; Tzartos, Socrates; Willcox, Nicholas; Kostera-Pruszczyk, Anna; Tallaksen, Chantal; Mantegazza, Renato; Berrih-Aknin, Sonia; Miller, Ariel

    2014-01-01

    Objective To identify novel genetic loci that predispose to early-onset myasthenia gravis (EOMG) applying a two-stage association study, exploration, and replication strategy. Methods Thirty-four loci and one confirmation loci, human leukocyte antigen (HLA)-DRA, were selected as candidate genes by team members of groups involved in different research aspects of MG. In the exploration step, these candidate genes were genotyped in 384 EOMG and 384 matched controls and significant difference in allele frequency were found in eight genes. In the replication step, eight candidate genes and one confirmation loci were genotyped in 1177 EOMG patients and 814 controls, from nine European centres. Results Allele frequency differences were found in four novel loci: CD86, AKAP12, VAV1, B-cell activating factor (BAFF), and tumor necrosis factor-alpha (TNF-α), and these differences were consistent in all nine cohorts. Haplotype trend test supported the differences in allele frequencies between cases and controls. In addition, allele frequency difference in female versus male patients at HLA-DRA and TNF-α loci were observed. Interpretation The genetic associations to EOMG outside the HLA complex are novel and of interest as VAV1 is a key signal transducer essential for T- and B-cell activation, and BAFF is a cytokine that plays important roles in the proliferation and differentiation of B-cells. Moreover, we noted striking epistasis between the predisposing VAV1 and BAFF haplotypes; they conferred a greater risk in combination than alone. These, and CD86, share the same signaling pathway, namely nuclear factor-kappaB (NFκB), thus implicating dysregulation of proinflammatory signaling in predisposition to EOMG. PMID:25356403

  16. Cognitive impairment as a central cholinergic deficit in patients with Myasthenia Gravis

    PubMed Central

    Kaltsatou, Antonia; Fotiou, Dimitris; Tsiptsios, Dimitris; Orologas, Anastasios

    2015-01-01

    Background The purpose of this study was to investigate with neurophysiological and neuropsychological methods such as pupillometry, cognitive test and Hamilton Depression Rating Scale (HAM-D) the hypothesis of Central Nervous System (CNS) cholinergic involvement in patients with Myasthenia Gravis (MG). Methods Thirty-two patients (32) with MG and a mean age of 51.1 ± 17.2 volunteered to participate in this investigation, while thirty-three (33) healthy subjects with a mean age of 50.2 ± 14.8 served as controls. All subjects underwent pupillometric measurements and performed the Wechsler Memory Scale (WMS) and HAM-D. The pupillometric indices studied were: 1) latency for the onset of constriction (T1), 2) maximum constriction velocity (VCmax) and 3) maximum constriction acceleration (ACmax). Results T1 was found significantly increased by 21.7% (p < 0.05) in MG patients as compared to healthy subjects. Conversely, VCmax and ACmax were significantly decreased in MG patients by 33.3% (p < 0.05) and 43.5% (p < 0.05) respectively, as opposed to healthy subjects. Additionally, MG patients showed significantly decreased score in WMS by 41.6% (p < 0.05) as compared to healthy controls. No significant difference was found for HAM-D between the two groups. Conclusions VCmax and ACmax are governed mainly by the action of the Parasympathetic Nervous System, through acetylcholine. The results of this study demonstrate that the CNS may be affected in MG and support the hypothesis that MG has central cholinergic effects manifested by cognitive dysfunction. PMID:26672759

  17. [Concurrence of myasthenia gravis, polymyositis, thyroiditis and eosinophilia in a patient with type B1 thymoma].

    PubMed

    Inoue, Manabu; Kojima, Yasuhiro; Shinde, Akiyo; Satoi, Hitoshi; Makino, Fumi; Kanda, Masutarou; Shibasaki, Hiroshi

    2007-07-01

    We presented a 43-year-old Japanese woman who acutely developed weakness of all extremities and difficulty in swallowing and drooping of eyelids, characterized by easy fatigability at the end of December, 2005. On general physical examination, she had moderate goiter. No cervical lymphadenopathy, cardiac murmur, or skin rash was noted. Neurologically, she had blepharoptosis, more on the right, only in the upright position with easy fatigability and marked weakness in the neck flexor, trunk, and all limb muscles much more proximally than distally. She had neither muscular atrophy nor upper motor neuron sign. Laboratory data showed slight leukocytosis with eosinophilia (up to 31%), and serum creatine kinase was markedly increased to over 2,000 IU/l. TSH receptor antibody (11.9%) and anti-acetylcholine receptor antibody (46.6 nmol/L) were also increased. Edrophonium test was positive. Electrophysiologically, muscle evoked potentials by repetitive motor nerve stimulation showed 13% and 50% waning in abductor pollicis brevis and deltoid muscle, respectively, at low frequency and no waxing at high frequency. Needle EMG showed fibrillation potentials and positive sharp waves in proximal muscles. Polymyositis was diagnosed by muscle biopsy which showed infiltration of lymphocytes in the endomysium and around non-necrotic muscle fibers. Upper arm muscle MRI showed multifocal high signal intensity lesions on T2-weighted images which were likely related to myositis. This finding is atypical for polymyositis. X-ray and CT of chest showed a mass lesion in the left pulmonary hilum, which was histologically diagnosed as type B1 thymoma. Thus, the present case had myasthenia gravis, polymyositis, thyroidititis and eosinophilia associated with type B1 thymoma. After the thymectomy, corticosteroid administration and immunoadsorption therapy, clinical symptoms and all laboratory abnormalities markedly improved. PMID:17710886

  18. Response to suxamethonium during propofol-fentanyl-N2O/O2 anaesthesia in a patient with active myasthenia gravis receiving long-term anticholinesterase therapy.

    PubMed

    Vanlinthout, L E; Robertson, E N; Booij, L H

    1994-06-01

    We describe the effect of repeated suxamethonium doses during propofol-fentanyl-N2O/O2 anaesthesia in a 29-year-old woman with active myasthenia gravis receiving chronic pyridostigmine therapy. Despite adequate pre-operative pseudocholinesterase activity, suxamethonium resistance occurred. Neither bradycardia nor residual neuromuscular block were seen after repeated doses of suxamethonium. PMID:8017595

  19. Severe congenital myasthenia gravis of the presynaptic type with choline acetyltransferase mutation in a Chinese infant with respiratory failure.

    PubMed

    Yeung, Wai L; Lam, Ching W; Fung, Lai W E; Hon, Kam L E; Ng, Pak C

    2009-01-01

    We report a severe case of congenital myasthenia gravis in a Chinese newborn who presented with complete ptosis, severe hypotonia, dysphagia and respiratory insufficiency with recurrent apnea that required mechanical ventilatory support since birth. Routine neurophysiologic studies, including the 3-Hz repetitive stimulation test and electromyogram were normal. Neostigmine and edrophonium tests were also negative. However, decremental response to 3-Hz stimulation became apparent after depleting the muscles with trains of 10-Hz stimuli for 10 min. The infant was subsequently confirmed to have heterozygous mutations in the choline acetyltransferase genes, p.T553N and p.S704P. Both missense mutations are novel mutations. The child remained on positive pressure ventilation at 3 years of age despite treatment with high-dose anticholinesterase. This case highlights the difficulty of making an early diagnosis based on clinical presentation and routine electrophysiologic tests, especially when neonatologists are not familiar with this condition. Further, as there are different genetic defects causing different types of congenital myasthenia gravis, anticholinesterase therapy may be beneficial to some but detrimental to others. Therefore, the exact molecular diagnosis is an important guide to therapy. A high index of suspicion coupled with extended electrodiagnostic tests in clinically suspected patients will ensure the selection of appropriate genetic molecular study for confirming the diagnosis. PMID:18797171

  20. Effects of the ß2-adrenoceptor agonist, albuterol, in a mouse model of anti-MuSK myasthenia gravis.

    PubMed

    Ghazanfari, Nazanin; Morsch, Marco; Tse, Nigel; Reddel, Stephen W; Phillips, William D

    2014-01-01

    The β2-adrenergic receptor agonist, albuterol, has been reported beneficial in treating several forms of congenital myasthenia. Here, for the first time, we examined the potential benefit of albuterol in a mouse model of anti-Muscle Specific Kinase (MuSK) myasthenia gravis. Mice received 15 daily injections of IgG from anti-MuSK positive patients, which resulted in whole-body weakness. At neuromuscular junctions in the tibialis anterior and diaphragm muscles the autoantibodies caused loss of postsynaptic acetylcholine receptors, and reduced the amplitudes of the endplate potential and spontaneous miniature endplate potential in the diaphragm muscle. Treatment with albuterol (8 mg/kg/day) during the two-week anti-MuSK injection series reduced the degree of weakness and weight loss, compared to vehicle-treated mice. However, the compound muscle action potential recorded from the gastrocnemius muscle displayed a decremental response in anti-MuSK-injected mice whether treated with albuterol or vehicle. Ongoing albuterol treatment did not increase endplate potential amplitudes compared to vehicle-treated mice nor did it prevent the loss of acetylcholine receptors from motor endplates. On the other hand, albuterol treatment significantly reduced the degree of fragmentation of endplate acetylcholine receptor clusters and increased the extent to which the remaining receptor clusters were covered by synaptophysin-stained nerve terminals. The results provide the first evidence that short-term albuterol treatment can ameliorate weakness in a robust mouse model of anti-MuSK myasthenia gravis. The results also demonstrate that it is possible for albuterol treatment to reduce whole-body weakness without necessarily reversing myasthenic impairment to the structure and function of the neuromuscular junction. PMID:24505322

  1. Effects of the ß2-Adrenoceptor Agonist, Albuterol, in a Mouse Model of Anti-MuSK Myasthenia Gravis

    PubMed Central

    Ghazanfari, Nazanin; Morsch, Marco; Tse, Nigel; Reddel, Stephen W.; Phillips, William D.

    2014-01-01

    The β2-adrenergic receptor agonist, albuterol, has been reported beneficial in treating several forms of congenital myasthenia. Here, for the first time, we examined the potential benefit of albuterol in a mouse model of anti-Muscle Specific Kinase (MuSK) myasthenia gravis. Mice received 15 daily injections of IgG from anti-MuSK positive patients, which resulted in whole-body weakness. At neuromuscular junctions in the tibialis anterior and diaphragm muscles the autoantibodies caused loss of postsynaptic acetylcholine receptors, and reduced the amplitudes of the endplate potential and spontaneous miniature endplate potential in the diaphragm muscle. Treatment with albuterol (8 mg/kg/day) during the two-week anti-MuSK injection series reduced the degree of weakness and weight loss, compared to vehicle-treated mice. However, the compound muscle action potential recorded from the gastrocnemius muscle displayed a decremental response in anti-MuSK-injected mice whether treated with albuterol or vehicle. Ongoing albuterol treatment did not increase endplate potential amplitudes compared to vehicle-treated mice nor did it prevent the loss of acetylcholine receptors from motor endplates. On the other hand, albuterol treatment significantly reduced the degree of fragmentation of endplate acetylcholine receptor clusters and increased the extent to which the remaining receptor clusters were covered by synaptophysin-stained nerve terminals. The results provide the first evidence that short-term albuterol treatment can ameliorate weakness in a robust mouse model of anti-MuSK myasthenia gravis. The results also demonstrate that it is possible for albuterol treatment to reduce whole-body weakness without necessarily reversing myasthenic impairment to the structure and function of the neuromuscular junction. PMID:24505322

  2. An acetylcholine receptor alpha subunit promoter confers intrathymic expression in transgenic mice. Implications for tolerance of a transgenic self-antigen and for autoreactivity in myasthenia gravis.

    PubMed

    Salmon, A M; Bruand, C; Cardona, A; Changeux, J P; Berrih-Aknin, S

    1998-06-01

    Myasthenia gravis (MG) is an autoimmune disease targeting the skeletal muscle acetylcholine receptor (AChR). Although the autoantigen is present in the thymus, it is not tolerated in MG patients. In addition, the nature of the cell bearing the autoantigen is controversial. To approach these questions, we used two lineages of transgenic mice in which the beta-galactosidase (beta-gal) gene is under the control of a 842-bp (Tg1) or a 3300-bp promoter fragment (Tg2) of the chick muscle alpha subunit AChR gene. In addition to expression in muscle cells, thymic expression was observed in both mouse lines (mainly in myoid cells in Tg1 and myoid cells and epithelial cells in Tg2). After challenge with beta-gal, Tg1 mice produced Th2-dependent anti-beta-gal antibodies, while Tg2 mice were almost unresponsive. By contrast, in a proliferation assay both Tg lines were unresponsive to beta-gal. Cells from Tg1 mice produce Th2-dependent cytokine whereas cells from Tg2 mice were nonproducing in response to beta-gal. These data indicate that the level of expression in Tg1 mice could be sufficient to induce tolerance of Th1 cells but not of Th2 cells, while both populations are tolerated in Tg2 mice. These findings are compatible with the hypothesis that AChR expression is not sufficiently abundant in MG thymus to induce a full tolerance. PMID:9616205

  3. Expression of nicotinic acetylcholine receptor subunits in HEp-2 cells for immunodetection of autoantibody specificities in sera from Myasthenia gravis patients.

    PubMed

    George, S; Noack, M; Vanek, M; Rentzsch, J; Röber, N; Conrad, K; Roggenbuck, D; Küpper, J-H

    2015-01-01

    Myasthenia gravis (MG) is an autoimmune disease characterized by the formation of pathogenic autoantibodies mostly targeting the nicotinic acetylcholine receptor (AChR). The AChR is composed of two alpha subunits and one subunit of each beta, delta and gamma (fetal AChR), or epsilon (adult AChR), respectively. Serological diagnostics is commonly done by radioimmunoassay (RIA). Here we used an indirect immunofluorescence assay with MG patient sera on transiently transfected HEp-2 cells expressing selected components of the AChR. Our data show that already 12 out of 13 MG patient sera showed autoantibody binding to HEp-2 cells transfected to express the alpha subunit solely. Interestingly, 11 out of 13 patient sera reacted positive with cells transfected to reconstitute the complete fetal AChR, but only 6 out of 13 sera showed positive signals with cells expressing the components of adult AChR. Moreover, there was no strict correlation of the serum concentration required to obtain clear-cut fluorescence signals to the antibody titer as measured by RIA. It will be an interesting topic to further investigate if the optimal serum dilution for indirect immunofluorescence as well as the autoantibody binding preferences to defined AChR subunits and to the adult versus the fetal receptor variant could provide additional predictive value in MG diagnostics. PMID:26410878

  4. Myasthenia gravis in patients with thymoma affects survival rate following extended thymectomy

    PubMed Central

    ZHANG, ZHEFENG; CUI, YOUBIN; JIA, RUI; XUE, LEI; LIANG, HUAGANG

    2016-01-01

    Thymomas are the most common adult tumors in the anterior mediastinal compartment, and a significant amount of thymomas are complicated by myasthenia gravis (MG). Extended thymectomy (ET) is the primary treatment method for thymomas and is used to completely resect possible ectopic thymus to avoid recurrence. Studies on the effect of MG in thymoma patients following ET are limited. The aim of the present study was to determine whether the presence of MG affects the prognosis of patients with thymoma. The present study consisted of 104 patients with thymoma that underwent ET; 61 men (58.7%) and 43 women (41.3%) (mean age, 54.6 years). In total, 38 patients had MG (36.5%). MG was most frequently observed in World Health Organization (WHO) classification type B2 thymoma compared with other types of thymoma. During the 5-year follow-up period, 11 patients succumbed to a recurrence of thymoma or respiratory failure due to MG. The overall 5-year survival rate in patients without MG or with MG was 89.1 and 76.0%, respectively. The overall survival (OS) rate in patients with Masaoka stages I + II and III + IV was 90.0 and 68.0%, respectively. The OS rate in patients with WHO type A + AB + B1 and type B2 + B3 was 96.9 and 76.8%, respectively. The patients with MG (P=0.026), Masaoka stages III + IV (P=0.008) and WHO type B2 + B3 (P=0.032) had a poorer prognosis compared with patients without these characteristics. Furthermore, multivariate analysis by Cox regression revealed that age [P=0.032; relative risk (RR)=1.097; 95% confidence interval (CI)=1.097–1.192] and MG (P=0.042; RR=0.167; 95% CI=0.037–0.940) significantly affected OS rate. In summary, ET is a reliable method for the treatment of thymoma. Long-term survival is expected for patients at early Masaoka stages, and for patients without MG. The prognosis of patients with thymomas with MG is poorer compared with patients without MG. The present findings provide useful information for the future management of

  5. [A CASE OF PULMONARY MYCOBACTERIUM ABSCESSUS INFECTION THAT DEVELOPED DURING IMMUNOSUPPRESSIVE THERAPY FOR MYASTHENIA GRAVIS WITH RECURRENT THYMOMA].

    PubMed

    Matsuse, Hiroto; Oshio, Takeshi; Kishimoto, Kumiko; Nakayama, Haruo

    2016-02-01

    A 58-year-old man developed cough, sputum, and low-grade fever during immunosuppressive treatment with corticosteroids and cyclosporine for myasthenia gravis with recurrent thymoma. Since chest CT revealed diffuse nodular opacities in both lung fields, he was referred to our department. Mycobacterium abscessus was repeatedly cultured from his sputum, and he was diagnosed with pulmonary M. abscessus infection. Although both chest radiological findings and clinical symptoms were mild, he required treatment with immunosuppressive agents and systemic anesthesia for resection of the recurrent thymoma. Based on complications and according to the patient's preference, oral treatment with clarithromycin 600 mg/day, levofloxacin 500 mg/day, and faropenem 600 mg/day was initiated on an outpatient basis. Following these treatments, his chest CT findings and clinical symptoms subsided, and the thymoma was successfully resected. Our experience with the present case suggests a possible treatment strategy for M. abscessus infection in immunocompromised and complicated cases. PMID:27263226

  6. Application of digital technology in the prosthodontic management of a patient with myasthenia gravis: A clinical report.

    PubMed

    AlHelal, Abdulaziz; Jekki, Rami; Richardson, Paul M; Kattadiyil, Mathew T

    2016-05-01

    Application of digital technology in the treatment of a patient with myasthenia gravis and an excessively resorbed mandibular residual alveolar ridge is presented. The patient requested replacement of worn maxillary and mandibular prostheses. Treatment involved fabricating a new maxillary complete denture that was similar in appearance to the one being replaced and rebasing the existing and clinically acceptable mandibular fixed framework. The interim phase of treatment involved fabricating a mandibular milled prosthesis similar in morphology to the existing fixed complete denture with computer-aided design and computer-aided manufacturing technology. This facilitated conversion of an interim prosthesis by using an orientation device and eliminated the need for the patient to adapt to an interim removable complete denture. PMID:26775246

  7. Morphological and Molecular Characterization of Exophiala polymorpha sp. nov. Isolated from Sporotrichoid Lymphocutaneous Lesions in a Patient with Myasthenia Gravis.

    PubMed

    Yong, Lee K; Wiederhold, Nathan P; Sutton, Deanna A; Sandoval-Denis, Marcelo; Lindner, Jonathan R; Fan, Hongxin; Sanders, Carmita; Guarro, Josep

    2015-09-01

    Exophiala species are capable of causing cutaneous and subcutaneous infections in immunocompromised patients. An Exophiala isolate was cultured from a biopsy specimen of a lesion on the forearm of a patient with myasthenia gravis. The patient also had lesions on the palm and distal aspects of the hand, which were successfully treated with a long-term course of itraconazole. A detailed morphological and molecular characterization of the isolate was undertaken. Phylogenetic analysis of the internal transcribed spacer region and portions of the β-tubulin and translation elongation factor 1-alpha genes indicated that the isolate was a novel species closely related to but genetically distinct from species within the Exophiala spinifera clade; the name Exophiala polymorpha sp. nov. is proposed. Morphologically, E. polymorpha most closely resembles E. xenobiotica but it differs in possessing phialides bearing prominent, wide collarettes, and it does not produce chlamydospores. PMID:26085612

  8. Morphological and Molecular Characterization of Exophiala polymorpha sp. nov. Isolated from Sporotrichoid Lymphocutaneous Lesions in a Patient with Myasthenia Gravis

    PubMed Central

    Yong, Lee K.; Sutton, Deanna A.; Sandoval-Denis, Marcelo; Lindner, Jonathan R.; Fan, Hongxin; Sanders, Carmita; Guarro, Josep

    2015-01-01

    Exophiala species are capable of causing cutaneous and subcutaneous infections in immunocompromised patients. An Exophiala isolate was cultured from a biopsy specimen of a lesion on the forearm of a patient with myasthenia gravis. The patient also had lesions on the palm and distal aspects of the hand, which were successfully treated with a long-term course of itraconazole. A detailed morphological and molecular characterization of the isolate was undertaken. Phylogenetic analysis of the internal transcribed spacer region and portions of the β-tubulin and translation elongation factor 1-alpha genes indicated that the isolate was a novel species closely related to but genetically distinct from species within the Exophiala spinifera clade; the name Exophiala polymorpha sp. nov. is proposed. Morphologically, E. polymorpha most closely resembles E. xenobiotica but it differs in possessing phialides bearing prominent, wide collarettes, and it does not produce chlamydospores. PMID:26085612

  9. Disease specific enrichment of circulating let-7 family microRNA in MuSK+ myasthenia gravis.

    PubMed

    Punga, Tanel; Bartoccioni, Emanuela; Lewandowska, Marta; Damato, Valentina; Evoli, Amelia; Punga, Anna Rostedt

    2016-03-15

    Myasthenia gravis (MG) patients with antibodies against the muscle specific tyrosine kinase (MuSK+) have predominantly involvement of cranio-bulbar muscles and do not display thymus pathology, as do acetylcholine receptor antibody seropositive (AChR+) MG patients. In search of novel biomarkers for MuSK+ MG, we evaluated circulating serum microRNAs. Four analyzed microRNAs were specifically elevated in MuSK+ MG patient serum samples: let-7a-5p, let-7f-5p, miR-151a-3p and miR-423-5p. The circulating microRNA profile in MuSK+ MG differs from the profile previously observed in the serum of AChR+ MG, thus indicating the etiological difference between these two entities. We propose that the identified microRNAs could serve as potential serum biomarkers for MuSK+ MG. PMID:26943954

  10. Pure red cell aplasia associated with malignant thymoma, myasthenia gravis, polyclonal large granular lymphocytosis and clonal thymic T cell expansion.

    PubMed Central

    Handa, S I; Schofield, K P; Sivakumaran, M; Short, M; Pumphrey, R S

    1994-01-01

    A case with the triad of pure red cell aplasia (PRCA), myasthenia gravis, and malignant thymoma is reported. There was a clonal proliferation of T cells within the thymoma, as demonstrated by a T cell antigen receptor (TCR) delta chain gene rearrangement. However, despite a large granular lymphocytosis, clonality could not be shown in the peripheral blood either before or after thymectomy. There was no evidence of human T cell lymphotrophic virus type 7 (HTLV1) infection. It is postulated that the clonal thymic T cell population secreted cytokine(s), which stimulated the polyclonal proliferation of large granular lymphocytes, which in turn suppressed erythropoiesis. Thymectomy removed the stimulus to the large granular lymphocytes and hence there was a resurgence of erythropoiesis. Images PMID:8089232

  11. [A case of radiation-related pneumonia and bilateral tension pneumothorax after extended thymectomy and adjuvant radiation for thymoma with myasthenia gravis].

    PubMed

    Nakasone, Etsuko; Nakayama, Masayuki; Bando, Masashi; Endo, Shunsuke; Hironaka, Mitsugu; Sugiyama, Yukihiko

    2010-08-01

    A 62-year-old man was admitted to our hospital with a 2-month history of progressive cough and dyspnea. He had undergone thymectomy for thymoma with myasthenia gravis. Adjuvant radiation of 50 Gy had been performed until 6 months before the symptoms developed. Chest computed tomography showed infiltrative findings even outside the irradiated area. We diagnosed radiation-related pneumonia, and 30 mg per day prednisolone was initiated. On the final day, he developed bilateral tension pneumothorax. After chest tube drainage, the right S5 bulla was resected with video-assisted thoracoscopic surgery (VATS). The right pneumothorax caused the bilateral tension pneumothorax, because the right and left thoracic cavity communicated in the anterior mediastinum after thymectomy. We should be aware of the risk of bilateral tension pneumothorax following radiation-related pneumonia after extended thymectomy and adjuvant radiation in patients with myasthenia gravis. PMID:20803975

  12. In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes.

    PubMed Central

    Brocke, S; Brautbar, C; Steinman, L; Abramsky, O; Rothbard, J; Neumann, D; Fuchs, S; Mozes, E

    1988-01-01

    To investigate which parts of the acetylcholine receptor are involved in the initiation and development of myasthenia gravis (MG), peptides representing different sequences of the human acetylcholine receptor alpha-subunit were synthesized. These peptides were tested for their ability to stimulate T cells of myasthenic patients and healthy control patients in proliferation assays and to bind to sera antibodies. Three of eight peptides discriminated significantly between the two groups in the proliferation assay, as well as in their ability to bind to serum antibodies. HLA-DR3 and DR5 were associated with proliferative responses to specific AChR peptides in the group of myasthenics. Acetylcholine receptor epitopes that might play a specific role in myasthenia gravis thus were demonstrated. PMID:2461962

  13. Myasthenia Gravis and the Tops and Bottoms of AChRs Antigenic Structure of the MIR and Specific Immunosuppression of EAMG Using AChR Cytoplasmic Domains

    PubMed Central

    Lindstrom, Jon; Luo, Jie; Kuryatov, Alexander

    2009-01-01

    The main immunogenic region (MIR), against which half or more of the autoantibodies to acetylcholine receptors (AChRs) in myasthenia gravis (MG) or experimental autoimmune MG (EAMG) are directed, is located at the extracellular end of α1 subunits. Rat monoclonal antibodies (mAbs) to the MIR efficiently compete with MG patient autoantibodies for binding to human muscle AChRs. Antibodies bound to the MIR do not interfere with cholinergic ligand binding or AChR function, but target complement and trigger antigenic modulation. Rat mAbs to the MIR also bind to human ganglionic AChR α3 subunits, but MG patient antibodies do not. By making chimeras of α1 subunits with α7 subunits or ACh binding protein, the structure of the MIR and its functional effects are being investigated. Many mAbs to the MIR bind only to the native conformation of α1 subunits because they bind to sequences that are adjacent only in the native structure. The MIR epitopes recognized by these mAbs are not recognized by most patient antibodies whose epitopes must be nearby. The presence of the MIR epitopes in α1/α7 chimeras greatly promotes AChR expression and sensitivity to activation. EAMG can be suppressed by treatment with denatured, bacterially expressed mixtures of extracellular and cytoplasmic domains of human α1, β1, γ, δ, and ε subunits. A mixture of only the cytoplasmic domains not only avoids the potential liability of provoking formation antibodies to pathologically significant epitopes on the extracellular surface, but also potently suppresses the development of EAMG. PMID:18567851

  14. HLA genotypes in Turkish patients with myasthenia gravis: comparison with multiple sclerosis patients on the basis of clinical subtypes and demographic features.

    PubMed

    Dönmez, Berril; Ozakbas, Serkan; Oktem, Mehmet Ali; Gedizlioglu, Muhtesem; Coker, Isil; Genc, Ahmet; Idiman, Egemen

    2004-07-01

    The nature and intensity of the association of myasthenia gravis (MG) with distinct human leukocyte antigens (HLA) haplotypes differ between ethnic populations. The aims of the present study were to examine the relationship between HLA class I and II haplotypes and MG; to show the HLA associations with various MG subsets; and to investigate the association between MG and clinical subgroups of multiple sclerosis (MS) regarding HLA haplotypes. A total of 66 patients with MG were enrolled onto the study. The mean age at onset was 42.01 years. A total of 122 clinically definite MS patients and 188 healthy subjects were examined as control groups. The present study clearly showed associations with HLA-DR3, -B8, -A1, and -A2 in MG. In patients with early-onset MG, associations with HLA-DR3, -B8, and -A2 were stronger. When compared with MS, in the MG group, there was still a strong association with -B8, -DR3, and -A1. In subgroup analysis, there was no difference between MG and primary progressive MS patients. On the basis of the presence of anti-AChR antibodies, there was a statistically significant association with HLA-DR3. On the basis of presence of thymoma, no HLA allele showed clear associations in MG patients with thymoma. This is the first study to examine the relationship between HLA haplotypes and MG in the Turkish population and to compare MG with another autoimmune disease, MS, on the basis of the HLA haplotypes. Further investigations with a larger population are required to explain this finding. PMID:15301866

  15. Increased expression of Toll-like receptors 7 and 9 in myasthenia gravis thymus characterized by active Epstein-Barr virus infection.

    PubMed

    Cavalcante, Paola; Galbardi, Barbara; Franzi, Sara; Marcuzzo, Stefania; Barzago, Claudia; Bonanno, Silvia; Camera, Giorgia; Maggi, Lorenzo; Kapetis, Dimos; Andreetta, Francesca; Biasiucci, Amelia; Motta, Teresio; Giardina, Carmelo; Antozzi, Carlo; Baggi, Fulvio; Mantegazza, Renato; Bernasconi, Pia

    2016-04-01

    Considerable data implicate the thymus as the main site of autosensitization to the acetylcholine receptor in myasthenia gravis (MG), a B-cell-mediated autoimmune disease affecting the neuromuscular junction. We recently demonstrated an active Epstein-Barr virus (EBV) infection in the thymus of MG patients, suggesting that EBV might contribute to the onset or maintenance of the autoimmune response within MG thymus, because of its ability to activate and immortalize autoreactive B cells. EBV has been reported to elicit and modulate Toll-like receptor (TLR) 7- and TLR9-mediated innate immune responses, which are known to favor B-cell dysfunction and autoimmunity. Aim of this study was to investigate whether EBV infection is associated with altered expression of TLR7 and TLR9 in MG thymus. By real-time PCR, we found that TLR7 and TLR9 mRNA levels were significantly higher in EBV-positive MG compared to EBV-negative normal thymuses. By confocal microscopy, high expression levels of TLR7 and TLR9 proteins were observed in B cells and plasma cells of MG thymic germinal centers (GCs) and lymphoid infiltrates, where the two receptors co-localized with EBV antigens. An increased frequency of Ki67-positive proliferating B cells was found in MG thymuses, where we also detected proliferating cells expressing TLR7, TLR9 and EBV antigens, thus supporting the idea that EBV-associated TLR7/9 signaling may promote abnormal B-cell activation and proliferation. Along with B cells and plasma cells, thymic epithelium, plasmacytoid dendritic cells and macrophages exhibited enhanced TLR7 and TLR9 expression in MG thymus; TLR7 was also increased in thymic myeloid dendritic cells and its transcriptional levels positively correlated with those of interferon (IFN)-β. We suggested that TLR7/9 signaling may be involved in antiviral type I IFN production and long-term inflammation in EBV-infected MG thymuses. Our overall findings indicate that EBV-driven TLR7- and TLR9-mediated innate immune

  16. [Myasthenia, from the internist's point of view].

    PubMed

    Eymard, B

    2014-07-01

    Myasthenia gravis is an autoimmune disease due to specific antibodies inducing a neuromuscular transmission defect causing muscle fatigability. If onset of the disease may be at any age, myasthenia gravis concerns mostly young adults, in majority females. The disease characteristic features are the following: ocular symptoms (ptosis or diplopia) as main initial manifestation, extension to other muscles in 80 % of the cases, variability of the deficit, effort induced worsening, successive periods of exacerbation during the disease course, severity depending on respiratory and swallowing impairment (if rapid worsening, a myasthenic crisis is to be suspected), association with thymoma in 20 % of patients and with other various autoimmune diseases, most commonly hyperthyroidism and Hashimoto's disease. Diagnosis relies on the clinical features, improvement with cholinesterase inhibitors, detection of specific autoantibodies (anti-AChR or anti-MuSK), and significant decrement evidenced by electrophysiological tests. The points concerning specifically the internist have been highlighted in this article: diagnostic traps, associated autoimmune diseases, including inflammatory myopathies that may mimic myasthenia gravis, adverse effects of medications commonly used in internal medicine, some of them inducing myasthenic syndromes. The treatment is well codified: the treatment is well codified: (1) respect of adverse drugs contra-indications, systematically use of cholinesterase inhibitors, (2) thymectomy if thymoma completed with radiotherapy if malignant, (3) corticosteroids or immunosuppressive agent in severe or disabling form, (4) intensive care unit monitoring, plasmapheresis or intravenous immunoglobulins for patients with myasthenic crisis. PMID:24112993

  17. Incidence and Prevalence of Myasthenia Gravis in Korea: A Population-Based Study Using the National Health Insurance Claims Database

    PubMed Central

    Park, Su-Yeon; Lee, Jin Yong

    2016-01-01

    Background and Purpose There have been a few national population-based epidemiological studies of myasthenia gravis (MG) with wide variation of incidence and prevalence rates worldwide. Herein we report the first nationwide population-based epidemiological study of MG in Korea. Methods We attempted to estimate the incidence and prevalence rates of MG using the Korean National Health Insurance claims database for 2010 to 2013. Cases with MG were defined as those having claim records with a principal diagnosis of MG and the prescription of acetylcholinesterase inhibitors or immunosuppressive agents including corticosteroids and azathioprine within 2 years after the diagnosis. The year 2010 was set as a washout period, such that patients were defined as incident cases if their first records of MG were observed in 2011. Results In 2011 there were 1,236 incident cases, and the standardized incidence rate was 2.44 per 100,000 person-years. The standardized prevalence rates were 9.67 and 10.66 per 100,000 persons in 2010 and 2011, respectively. The incidence and prevalence rates peaked in the elderly population aged 60 to 69 years for both sexes. Conclusions This is one of the largest national population-based epidemiological studies of MG, and it has confirmed the high incidence and prevalence rates of MG in the elderly population of South Korea. PMID:27165426

  18. T helper cell recognition of muscle acetylcholine receptor in myasthenia gravis. Epitopes on the gamma and delta subunits.

    PubMed Central

    Manfredi, A A; Protti, M P; Dalton, M W; Howard, J F; Conti-Tronconi, B M

    1993-01-01

    We tested the response of CD4+ cells and/or total lymphocytes from the blood of 22 myasthenic patients and 10 healthy controls to overlapping synthetic peptides, 20 residues long, to screen the sequence of the gamma and delta subunits of human muscle acetylcholine receptor (AChR). The gamma subunit is part of the AChR expressed in embryonic muscle and is substituted in the AChRs of most adult muscles by an epsilon subunit. The delta subunit is present in both embryonic and adult AChRs. Adult extrinsic ocular muscles, which are preferentially and sometimes uniquely affected by myasthenic symptoms, and thymus, which has a still obscure but important role in the pathogenesis of myasthenia gravis, express the embryonic gamma subunit. Anti-AChR CD4+ responses were more easily detected after CD8+ depletion. All responders recognized epitopes on both the gamma and delta subunits and had severe symptoms. In four patients the CD4+ cell response was tested twice, when the symptoms were severe and during a period of remission. Consistently, the response was only detectable, or larger, when the patients were severely affected. Images PMID:7688757

  19. Myopathic changes detected by quantitative electromyography in patients with MuSK and AChR positive myasthenia gravis.

    PubMed

    Nikolic, Ana; Basta, Ivana; Stojanovic, Vidosava Rakocevic; Stevic, Zorica; Peric, Stojan; Lavrnic, Dragana

    2016-05-01

    Myopathic changes are frequent a electrophysiological finding in patients with muscle specific tyrosine kinase (MuSK) positive myasthenia gravis (MG). The aim of this study was to explore the importance of quantitative electromyography (EMG) in the detection of myopathic changes in MuSK MG patients. Classical and quantitative EMG were performed in 31 MuSK and 28 acetylcholine receptor (AChR) positive MG patients, matched by sex, age, disease duration and severity. Classical EMG revealed the presence of myopathic changes more frequently in MuSK MG compared to AChR MG patients, especially in the facial muscles. Quantitative EMG registered myopathic lesions more frequently than classical EMG, but the frequency was similar between MuSK and AChR MG patients. Quantitative EMG revealed myopathic changes in the majority of both MuSK and AChR positive MG patients. This examination is sensitive, but it cannot be used to differentiate between MG patients belonging to the different disease groups. It should not be used in isolation. Rather, it should complement classical EMG in the detection of myopathic changes. PMID:26778359

  20. Preoperative Anxiety in Patients With Myasthenia Gravis and Risk for Myasthenic Crisis After Extended Transsternal Thymectomy: A CONSORT Study.

    PubMed

    Zou, Jianyong; Su, Chunhua; Lun, Xueping; Liu, Weibing; Yang, Weiling; Zhong, Beilong; Zhu, Haoshuai; Lei, Yiyan; Luo, Honghe; Chen, Zhenguang

    2016-03-01

    A thymectomy can ameliorate the symptoms of myasthenia gravis (MG) and prevent the progression of ocular MG (OMG) to generalized MG (GMG). However, postoperative myasthenic crisis (POMC) is a serious post-thymectomy complication. Preoperative anxiety (POA) is common but typically neglected in MG patients. The association of POA with POMC has not yet been examined.From June 2007 to December 2013, 541 cases of MG were admitted to the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). All cases underwent extended transsternal thymectomy (ETT). The clinical and pathological characteristics of these patients, including POA and POMC, were analyzed.A total of 179 patients experienced POA and 67 patients experienced POMC. Patients with POA were more likely to have POMC, a thymoma, and an ectopic thymus. Univariate analysis showed that POMC correlated with POA, presence of an ectopic thymus, dose of pyridostigmine bromide (PYR), presence of a thymoma, MGFA stage, preoperative myasthenic crisis, and postoperative pneumonia. Multivariate logistic regression analysis showed that the independent risk factors for POMC were POA, preoperative myasthenic crisis, higher dose of PYR, and postoperative pneumonia.Our results suggest that clinicians should consider the risk factors for POMC-especially preoperative anxiety-before performing a thymectomy in patients with MG. PMID:26962777

  1. Enhancement of noradrenergic neural transmission: an effective therapy of myasthenia gravis: a report on 52 consecutive patients.

    PubMed

    Lechin, F; van der Dijs, B; Pardey-Maldonado, B; John, E; Jimenez, V; Orozco, B; Baez, S; Lechin, M E

    2000-01-01

    Neurochemical, neuroautonomic and neuropharmacological assessments carried out on all our myasthenia gravis (MG) patients showed that they presented a neural sympathetic deficit plus excessive adrenal-sympathetic activity. These abnormalities were registered during the basal (supine-resting) state, as well as after several stress tests (orthostasis, exercise, oral glucose and buspirone). In addition, MG patients showed increased levels of free-serotonin (f5HT) in the plasma, supposedly associated with the increased platelet aggregability which we found in all MG patients. As the above trio of neurochemical disorders (low noradrenergic-activity + high adrenergic-activity + increased f-5HT plasma levels) is known to favor Th-1 immunosuppression + Th-2 predominance, we outlined a neuropharmacological strategy for reverting the above neurochemical disorder. This treatment provoked sudden (acute), and late sustained improvements. Acute effects have been attributed to the increase of alpha-1 activity at the spinal motoneuron level. Late improvements always paralleled a significant normalization of immunological disorders. Complete normalization was registered only in non-thymectomized MG patients. PMID:11508327

  2. Clinical Outcomes of Myasthenia Gravis with Thymoma and Thymic Hyperplasia Undergoing Extended Transsternal Thymectomy: A Single-Center Experience

    PubMed Central

    Nazarbaghi, Surena; Amiri-Nikpour, Mohammad Reza; Mahmodlou, Rahim; Arjmand, Nasim; Rezaei, Yousef

    2015-01-01

    Background: Despite the widespread use of thymectomy in myasthenia gravis (MG) patients, it has remained controversial as to whether this procedure is of a similar efficacy and clinical outcome among MG patients with thymoma and thymic hyperplasia. Aim: We sought to determine the long-term clinical outcomes of MG patients who received extended transsternal thymectomy associated with pyridostigmine and prednisolone postoperatively. Materials and Methods: In a retrospective study from January 1999 to December 2013, MG patients who underwent thymectomy were followed up. Out of 41 MG patients admitted in our center, 25 patients had undergone thymectomy adjunctive to pyridostigmine and prednisolone therapy postoperatively. The primary endpoints included improvement in individual diplopia, ptosis, dysphagia, dysarthria, dyspnea, and limb weakness. In addition, according to the MG Foundation of America (MGFA) criteria, response to therapy was defined as complete stable remission (CSR), pharmacologic remission (PR), and minimal manifestation (MM) as secondary endpoints. Results: Majority of the patients were male (60%) and the mean age of the patients was 32.2 ± 13.9 years. Fifteen (60%) and 10 patients (40%) had thymoma and thymic hyperplasia, respectively. All the patients were followed up during a mean period of of 86.9 ± 50.3 months (minimum 10 months and maximum 168 months). The rates of CSR, PR, and MM were comparable between the thymoma and thymic hyperplasia groups (P = 0.584). Based on the Kaplan Meier analysis, the probabilities of CSR, PR, and MM were not significantly different between patients with thymoma and thymic hyperplasia. Conclusion: The extended transsternal thymectomy, along with the postoperative regimen of pyridostigmine and prednisolone was associated with a high rate of clinical improvement among MG patients with thymoma or thymic hyperplasia. PMID:26713298

  3. [Localization of binding sites in rat muscles and brain for cobra neurotoxin and serum immunoglobulins from patients with myasthenia].

    PubMed

    Smirnov, V A; Vladeeva, N V; Lobzin, V S; Paniukov, A N

    1986-09-01

    Using the immunohistochemical technique, it was revealed that serum immunoglobulins of patients with myasthenia gravis (Ig) were irreversibly attached to the myoneuronal connections of the rat intercostal muscles like the marker of the nicotin cholinireceptors--the cobra venom neurotoxin (CT). In addition, Ig differs from CT in the binding to nervous cells of the claustrum and diencephalon reticular formation and with certain cells of the nucleus caudatus and hemispheric cerebral cortex. It is suggested that the autoimmune processes in patients with myasthenia gravis do not only involve myoneuronal connection but also participate in central mechanisms of the disease genesis. PMID:3756323

  4. Thymic abnormalities: antigen or antibody? Response to thymectomy in myasthenia gravis.

    PubMed

    Penn, A S; Jaretzki, A; Wolff, M; Chang, H W; Tennyson, V

    1981-01-01

    The therapeutic value of thymectomy for myasthenia is still questioned although it retains an important place among management modalities that strive for sustained remission. Questions derive from uncertainty as to appropriate timing, variable extent of resection and quantitation of response. Forty-seven patients, followed one to seven years, underwent an extended transsternal or combined transcervical-transsternal procedure with anterior mediastinal exenteration. Sixteen have been in complete remission from six months to six years, four are asymptomatic on occasional pyridostigmine and eight are significantly improved. Evaluation of thymic pathology (hyperplasic, involuted areas, and thymoma) included a search for thymic myoid cells by fluorescence cytochemistry. Antibodies to acetylcholine receptor present in 38 of 43, decreased post-operatively to normal in four, by 50% to 80% in 14, by 20 to 50% in three and were unchanged in 14. Most remissions occurred in young women with noninvoluted hyperplastic glands and variably high anti-AChR titers which dropped toward normal in seven of 15. These results encourage us to utilize this procedure routinely. PMID:6951500

  5. MYASTHENIA GRAVIS—Problems in Diagnosis

    PubMed Central

    Herrmann, Christian; Rose, Augustus S.

    1957-01-01

    The possibility of myasthenia gravis must be considered in patients persistently complaining of weakness and fatigue. There may be many difficulties and pitfalls in differentiating myasthenia gravis from other disorders in which muscular weakness is a common complaint. Observation of a group of 36 patients with myasthenia gravis, and another group of 30 cases involving the differential diagnosis of myasthenia gravis, led to a conclusion that a physician should apply criteria carefully before arriving at a diagnosis of myasthenia gravis and instituting drug therapy, since nonmyasthenics may frequently respond with subjective improvement temporarily following administration of cholinergic drugs. Myasthenia gravis may be a more common disorder than was suspected in the past. PMID:13489495

  6. Spontaneous remission in canine myasthenia gravis: implications for assessing human MG therapies.

    PubMed

    Shelton, G D; Lindstrom, J M

    2001-12-11

    The natural course of autoimmune canine MG was determined in 53 dogs with muscular weakness and a positive acetylcholine receptor antibody titer. Dogs were treated with anticholinesterase therapy, without immunosuppression. Spontaneous clinical and immunologic remission occurred in 47 of 53 dogs within an average of 6.4 months. Neoplasia was identified in the six dogs that did not spontaneously remit. This study questions the value of using canine MG in studies designed to assess the effect of immunotherapies. PMID:11739846

  7. Video-assisted thoracoscopic surgery versus sternotomy in thymectomy for thymoma and myasthenia gravis

    PubMed Central

    Woo, Edwin

    2016-01-01

    Thymectomy involves the removal of all the soft tissue in the pre-vascular plane of the anterior mediastinum between the two phrenic nerves. Surgical success in controlling myasthenia and the most important factor influencing survival in patients with thymoma depends on complete clearance of thymic tissue. Currently there is a perception that the open (median sternotomy) approach offers better visualisation of the thymic tissue. This perceived advantage is thought to justify the invasive nature of the procedure associated with increased morbidity. Video-assisted thoracoscopic surgery (VATS) for thymectomy has evolved significantly over the last decade, including bilateral and unilateral VATS (either left or right) approaches. The laterality of the approach remains largely on surgeon preferences, with the decision influenced by their experience and training. VATS offers superior illumination and magnification, particularly with the availability of advanced cameras with variable angles that provide better exposure and lighting of the operative field. The use of three-dimensional-operating imaging has also revolutionised the VATS technique. VATS thymectomy is a superior and radical technique in minimising access trauma and removing all thymic tissue that may be scattered in the anterior mediastinum and cervical fat. Other advantages of VATS include less intraoperative blood loss, early removal of chest drains, less requirement for blood products, decreased inflammatory cytokine response, shorter hospital stay and superior cosmesis. There is also a decreased risk of respiratory and cardiac related complications compared to the open (sternotomy) technique. Furthermore, no significant difference has been found in long-term complications and survival rate between VATS and open approaches. Subsequently, the VATS approach should be encouraged as more surgeons are adopting the minimally invasive practice as routine. PMID:26904429

  8. A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis

    PubMed Central

    2011-01-01

    Background Long-term immunosuppression is often required in myasthenia gravis (MG). There are no published trials using methotrexate (MTX) in MG. The steroid-sparing efficacy of azathioprine (AZA) has been demonstrated after 18-months of starting therapy. However, AZA is considered expensive in Africa. We evaluated the steroid-sparing efficacy of MTX (17.5 mg weekly) compared with AZA (2.5 mg/kg daily) in subjects recently diagnosed with generalized MG by assessing their average monthly prednisone requirements. Methods The primary outcome was the average daily prednisone requirement by month between the two groups. Prednisone was given at the lowest dose to manage MG symptoms and adjusted as required according to protocol. Single-blinded assessments were performed 3-monthly for 2-years to determine the quantitative MG score and the MG activities of daily living score in order to determine those with minimal manifestations of MG. Results Thirty-one subjects (AZA n = 15; MTX n = 16) satisfied the inclusion criteria but only 24 were randomized. Baseline characteristics were similar. There was no difference between the AZA- and MTX-groups in respect of prednisone dosing (apart from months 10 and 12), in quantitative MG Score improvement, proportions in sustained remission, frequencies of MG relapses, or adverse reactions and/or withdrawals. The MTX-group received lower prednisone doses between month 10 (p = 0.047) and month 12 (p = 0.039). At month 12 the prednisone dose per kilogram bodyweight in the MTX-group (0.15 mg/kg) was half that of the AZA-group (0.31 mg/kg)(p = 0.019). Conclusions This study provides evidence that in patients with generalized MG methotrexate is an effective steroid-sparing agent 10 months after treatment initiation. Our data suggests that in generalized MG methotrexate has similar efficacy and tolerability to azathioprine and may be the drug of choice in financially constrained health systems. Trial registration SANCTR:DOH-27-0411-2436 PMID

  9. Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK

    PubMed Central

    Yilmaz, Vuslat; Oflazer, Piraye; Aysal, Fikret; Durmus, Hacer; Poulas, Kostas; Yentur, Sibel P.; Gulsen-Parman, Yesim; Tzartos, Socrates; Marx, Alexander; Tuzun, Erdem; Deymeer, Feza; Saruhan-Direskeneli, Güher

    2015-01-01

    Neuromuscular transmission failure in myasthenia gravis (MG) is most commonly elicited by autoantibodies (ab) to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON). Peripheral blood mononuclear cells (PBMC) were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK-MG patients

  10. Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK.

    PubMed

    Yilmaz, Vuslat; Oflazer, Piraye; Aysal, Fikret; Durmus, Hacer; Poulas, Kostas; Yentur, Sibel P; Gulsen-Parman, Yesim; Tzartos, Socrates; Marx, Alexander; Tuzun, Erdem; Deymeer, Feza; Saruhan-Direskeneli, Güher

    2015-01-01

    Neuromuscular transmission failure in myasthenia gravis (MG) is most commonly elicited by autoantibodies (ab) to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON). Peripheral blood mononuclear cells (PBMC) were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK-MG patients

  11. Individual germinal centres of myasthenia gravis human thymuses contain polyclonal activated B cells that express all the Vh and Vk families.

    PubMed Central

    Guigou, V; Emilie, D; Berrih-Aknin, S; Fumoux, F; Fougereau, M; Schiff, C

    1991-01-01

    Using in situ hybridization, we analysed the immunoglobulin repertoire expressed by the B cells present in myasthenia gravis thymuses from four patients. B cells, mostly in activated state, were clustered in germinal centres, in which multiple isotypes were identified. A majority of cells expressed IgG as compared with IgM, with a roughly similar contribution of kappa and lambda chains. Hybridization with the six VH and the 4 VK human family probes was observed in serial sections, providing additional evidence that individual germinal centres were polyclonal. The thymic B cell repertoire closely reflected the VH and the VK family usage of normal peripheral blood lymphocytes with the preferential utilization of VH3, VK1 and VK3. Images Fig. 1 Fig. 2 PMID:1899630

  12. Diagnosis of myasthenia gravis: Comparison of anti-nicotinic acetyl choline receptor antibodies, repetitive nerve stimulation and Neostigmine tests at a tertiary neuro care centre in India, a ten year study.

    PubMed

    Patil, Shripad A; Bokoliya, Suresh C; Nagappa, Madhu; Taly, Arun B

    2016-03-15

    Anti-nicotinic AChR antibodies (Anti-nAChR antibodies), Repetitive Nerve Stimulation (RNS) and Neostigmine test are used for diagnosis of myasthenia gravis (MG). We compared their diagnostic agreement in a cohort of 486 MG patients over a period of ten years. Anti-nAChR antibodies, RNS and Neostigmine test showed positivity of 57.36%, 51.78%, and 93.4% respectively in ocular myasthenia and 93.77%, 82.35%, and 97.92% respectively in generalized myasthenia group. Neostigmine test showed higher positivity than anti-nAChR antibodies and RNS test in both groups. A marginal to fair agreement was observed between these tests highlighting their significance in the diagnosis of the disease. PMID:26943963

  13. Ocular Myasthenia Gravis

    MedlinePlus

    ... involved. However, this is not completely understood. One hypothesis is that patients may simply notice eye weakness ... in other muscle groups in the body. Another hypothesis is that the eye and eyelid muscles are ...

  14. Myasthenia Gravis Fact Sheet

    MedlinePlus

    ... Plasmapheresis (PLAZ-muh-FUR-uh-suhss) or plasma exchange. This procedure removes abnormal antibodies from the blood. ... above — in particular, intravenous immune globulin and plasma exchange — can reverse the severe weakness of a myasthenic ...

  15. Myasthenia Gravis Tests

    MedlinePlus

    ... of those with MG who have an enlarged thymus gland and indicate a significantly increased likelihood of the ... chest CT (computed tomography)—to detect an enlarged thymus gland or thymoma. A brain and eye orbit MRI ( ...

  16. Nutrition and Myasthenia Gravis

    MedlinePlus

    ... and to improve their lives through programs of patient services, public information, medical research, professional education, advocacy and patient care. This publication is intended to provide the ...

  17. Employees with Myasthenia Gravis

    MedlinePlus

    ... of America, 2001). MG and the Americans with Disabilities Act Is MG a disability under the ADA? The ADA does not contain a list of medical conditions that constitute disabilities. Instead, the ADA has a general definition of ...

  18. Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment

    PubMed Central

    Im, Sin-Hyeog; Barchan, Dora; Fuchs, Sara; Souroujon, Miriam C.

    1999-01-01

    Myasthenia gravis (MG) is an autoimmune disorder in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. In an attempt to develop an antigen-specific therapy for MG, we administered a nonmyasthenogenic recombinant fragment of AChR orally to rats. This fragment, corresponding to the extracellular domain of the human AChR α-subunit (Hα1-205), protected rats from subsequently induced experimental autoimmune myasthenia gravis (EAMG) and suppressed ongoing EAMG when treatment was initiated during either the acute or chronic phases of disease. Prevention and suppression of EAMG were accompanied by a significant decrease in AChR-specific humoral and cellular responses. The underlying mechanism for the Hα1-205–induced oral tolerance seems to be active suppression, mediated by a shift from a T-helper 1 (Th1) to a Th2/Th3 response. This shift was assessed by changes in the cytokine profile, a deviation of anti-AChR IgG isotypes from IgG2 to IgG1, and a suppressed AChR-specific delayed-type hypersensitivity response. Our results in experimental myasthenia suggest that oral administration of AChR-specific recombinant fragments may be considered for antigen-specific immunotherapy of myasthenia gravis. J. Clin. Invest. 104:1723–1730 (1999). PMID:10606626

  19. Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment.

    PubMed

    Im, S H; Barchan, D; Fuchs, S; Souroujon, M C

    1999-12-01

    Myasthenia gravis (MG) is an autoimmune disorder in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. In an attempt to develop an antigen-specific therapy for MG, we administered a nonmyasthenogenic recombinant fragment of AChR orally to rats. This fragment, corresponding to the extracellular domain of the human AChR alpha-subunit (Halpha1-205), protected rats from subsequently induced experimental autoimmune myasthenia gravis (EAMG) and suppressed ongoing EAMG when treatment was initiated during either the acute or chronic phases of disease. Prevention and suppression of EAMG were accompanied by a significant decrease in AChR-specific humoral and cellular responses. The underlying mechanism for the Halpha1-205-induced oral tolerance seems to be active suppression, mediated by a shift from a T-helper 1 (Th1) to a Th2/Th3 response. This shift was assessed by changes in the cytokine profile, a deviation of anti-AChR IgG isotypes from IgG2 to IgG1, and a suppressed AChR-specific delayed-type hypersensitivity response. Our results in experimental myasthenia suggest that oral administration of AChR-specific recombinant fragments may be considered for antigen-specific immunotherapy of myasthenia gravis. PMID:10606626

  20. Ephedrine as add-on therapy for patients with myasthenia gravis: protocol for a series of randomised, placebo-controlled n-of-1 trials

    PubMed Central

    Vrinten, Charlotte; Lipka, Alexander F; van Zwet, Erik W; Schimmel, Kirsten J M; Cornel, Martina C; Kuijpers, Marja R; Hekster, Yechiel A; Weinreich, Stephanie S; Verschuuren, Jan J G M

    2015-01-01

    Introduction Myasthenia gravis (MG), a rare neuromuscular disease, is often initially treated using acetylcholinesterase inhibitors. Patients who do not respond adequately depend on the use of corticosteroids or other immunosuppressive medication, but these may have serious side effects. Clinical observations suggest that ephedrine can diminish, postpone or even prevent the need for immunosuppressive therapy when added to acetylcholinesterase inhibitors or low-dose prednisone. In the Netherlands, ephedrine is not licensed for MG nor is reimbursement guaranteed. MG is a rare condition, and ephedrine might be indicated only in a subset of patients. Thus, randomised controlled trials comparing large groups are difficult to conduct. We, therefore, aim to aggregate data from a small series of n-of-1 trials (also known as single patient trials) to assess the effect of ephedrine as add-on treatment for MG. Methods and analysis Single-centre, placebo-controlled, double-blind, randomised, multiple crossover n-of-1 studies in 4 adult patients with generalised MG who show inadequate improvement on pyridostigmine and/or immunosuppressive drugs. Each n-of-1 trial has 3 cycles of two 5-day intervention periods. Treatment: 25 mg ephedrine or placebo, twice daily. Main outcome measure: Quantitative Myasthenia Gravis (QMG) test. Statistical analysis: fixed effects linear model for QMG for all patients combined. Secondary outcome measures: Clinical: effects on MG-Composite and MG-Activities of Daily Living (MG-ADL) scales; QMG at individual level; adverse events. Acceptability of trial design: number of patients eligible and enrolled; number of treatment cycles completed; patients’ and caregivers’ experiences. Ethics and dissemination This study was approved by the Medical Ethics Committee of Leiden University Medical Center, No. P14.108. Results of the trial will be reported in a peer-reviewed publication. Regulatory stakeholders will comment on the suitability of the trial

  1. Autoimmune disorders

    MedlinePlus

    ... Multiple sclerosis Myasthenia gravis Pernicious anemia Reactive arthritis Rheumatoid arthritis Sjögren syndrome Systemic lupus erythematosus Type I diabetes Symptoms Symptoms will vary based on the type ...

  2. Estimation of the success rate of anesthetic management for thymectomy in patients with myasthenia gravis treated without muscle relaxants: a retrospective observational cohort study.

    PubMed

    Fujita, Yoshihito; Moriyama, Satoru; Aoki, Satoshi; Yoshizawa, Saya; Tomita, Maiko; Kojima, Taiki; Mori, Yukiko; Takeuchi, Naoko; So, Min-Hye; Yano, Motoki; Sobue, Kazuya

    2015-10-01

    Although maintaining anesthesia for myasthenia gravis (MG) with minimal muscle relaxants (MR) is common, the success rate of anesthetic management for MG without MR is not clear. We therefore retrospectively examined the success rate of anesthetic management for MG without MR among 66 consecutive cases of thymectomy for MG performed at our hospital between January 2004 and April 2010, before approval of using sugammadex. A total of 60 patients (90.9 %) were treated without MR (N group). Among the 60 cases, 17 (28.3 %) patients were not extubated in the operating room due to postoperative respiratory depression or other reasons. Therefore, the success rate of anesthetic management for thymectomy in patients with MG without treating MR was 71.7 % (43/60) [95 % confident interval (CI): 65.9-77.5 %]. The reasons for using MR included coughing at intubation in one case, bucking during surgery in two cases, and MR was considered to be safer by the attending anesthesiologist in three cases. The number of cases of impossible extubation requiring ventilation on that day was three in the N group and none in the R group. Finally, the success rate of anesthetic management for MG without MR was estimated to be 71.1 % (95 % CI: 65.9-77.5 %). PMID:25796520

  3. Epitopes on the beta subunit of human muscle acetylcholine receptor recognized by CD4+ cells of myasthenia gravis patients and healthy subjects.

    PubMed Central

    Moiola, L; Karachunski, P; Protti, M P; Howard, J F; Conti-Tronconi, B M

    1994-01-01

    We investigated the sequence regions of the human muscle acetylcholine receptor (AChR) beta subunit forming epitopes recognized by T helper cells in myasthenia gravis (MG), using overlapping synthetic peptides, 20 residues long, which screened the sequence of the AChR beta subunit. Since CD4+ lymphocytes from MG patients' blood did not respond to the peptides, we attempted propagation of beta subunit-specific T lines from six MG patients and seven healthy controls by cycles of stimulation of blood lymphocytes with the pooled peptides corresponding to the beta subunit sequence. CD4+ T lines were obtained from four patients and three controls. They secreted IL-2, not IL-4, suggesting that they comprised T helper type 1 cells. The T lines from MG patients could be propagated for several months. Three lines were tested with purified bovine muscle AChR and cross-reacted well with this antigen. All T lines were tested with the individual synthetic peptides present in the pool corresponding to the beta subunit sequence. Several beta subunit peptide sequences were recognized. Each line had an individual pattern of peptides recognition, but three sequence regions (peptides beta 181-200, beta 271-290, and the overlapping peptides beta 316-335 and beta 331-350) were recognized by most MG lines. The beta subunit-specific T lines from controls could be propagated for < 5 wk. Each line recognized several peptides, which frequently included the immunodominant regions listed above. Images PMID:7510715

  4. Myasthenia Gravis—Current Concepts

    PubMed Central

    Herrmann, Christian; Lindstrom, Jon M.; Keesey, John C.; Mulder, Donald G.

    1985-01-01

    An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Associate Professor of Medicine. Current findings indicate that autoimmune myasthenia gravis is an acquired immune complex disorder of neuromuscular transmission in voluntary striated muscle. There is a break in immunologic tolerance leading to blocking and degradation of acetylcholine receptors, together with widening of the synaptic cleft associated with partial destruction, simplification and shortening of the postjunctional membrane. Thymic hyperplasia and thymoma may be present. A decremental response to nerve-muscle stimulation, blocking and jitter on single-fiber electromyography and circulating antibodies to acetylcholine receptor are detectable in most patients with generalized weakness. Although the cause of this abnormal immunologic mechanism remains to be discovered, anticholinesterases, corticosteroids, immunosuppressants, plasmapheresis or thymectomy (individually or in combination) provide control and better prognosis in most patients. ImagesFigure 1. PMID:3895751

  5. Thyroid autoimmunity and polyglandular endocrine syndromes.

    PubMed

    Wémeau, Jean-Louis; Proust-Lemoine, Emmanuelle; Ryndak, Amélie; Vanhove, Laura

    2013-01-01

    Even though autoimmune thyroiditis is considered as the most emblematic type of organ-specific autoimmune disorder of autoimmunity, autoimmune thyroid diseases can be associated with other autoimmune endocrine failures or non-endocrine diseases (namely vitiligo, pernicious anemia, myasthenia gravis, autoimmune gastritis, celiac disease, hepatitis). Thyroid disorders, which are the most frequent expression of adult polyendocrine syndrome type 2, occur concomitantly with or secondarily to insulinodependent diabetes, premature ovarian failure, Addison's disease (Schmidt syndrome, or Carpenter syndrome if associated with diabetes). Testicular failure and hypoparathyroidism are unusual. The disease is polygenic and multifactorial. Disorders of thyroid autoimmunity are, surprisingly, very rare in polyendocrine syndrome type 1 (or APECED) beginning during childhood. They are related to mutations of the AIRE gene that encodes for a transcriptional factor implicated in central and peripheral immune tolerance. Hypothyroidism can also be observed in the very rare IPEX and POEMS syndromes. PMID:23624130

  6. Myf5 and Myogenin in the development of thymic myoid cells - Implications for a murine in vivo model of myasthenia gravis.

    PubMed

    Hu, Bo; Simon-Keller, Katja; Küffer, Stefan; Ströbel, Philipp; Braun, Thomas; Marx, Alexander; Porubsky, Stefan

    2016-03-01

    Myasthenia gravis (MG) is caused by autoantibodies against the neuromuscular junction of striated muscle. Most MG patients have autoreactive T- and B-cells directed to the acetylcholine receptor (AChR). To achieve immunologic tolerance, developing thymocytes are normally eliminated after recognition of self-antigen-derived peptides. Presentation of muscle-specific antigens is likely achieved through two pathways: on medullary thymic epithelial cells and on medullary dendritic cells cross-presenting peptides derived from a unique population of thymic myoid cells (TMC). Decades ago, it has been hypothesized that TMC play a key role in the induction of immunological tolerance towards skeletal muscle antigens. However, an experimental model to address this postulate has not been available. To generate such a model, we tested the hypothesis that the development of TMC depends on myogenic regulatory factors. To this end, we utilized Myf5-deficient mice, which lack the first wave of muscle cells but form normal skeletal muscles later during development, and Myogenin-deficient mice, which fail to form differentiated myofibers. We demonstrate for the first time that Myf5- and Myogenin-deficient mice showed a partial or complete, respectively, loss of TMC in an otherwise regularly structured thymus. To overcome early postnatal lethality of muscle-deficient, Myogenin-knockout mice we transplanted Myogenin-deficient fetal thymuses into Foxn1(nu/nu) mice that lack their own thymus anlage. We found that the transplants are functional but lack TMC. In combination with established immunization strategies (utilizing AChR or Titin), this model should enable us in the future testing the hypothesis that TMC play an indispensable role in the development of central tolerance towards striated muscle antigens. PMID:26708556

  7. Patient autoantibodies deplete postsynaptic muscle-specific kinase leading to disassembly of the ACh receptor scaffold and myasthenia gravis in mice.

    PubMed

    Cole, R N; Ghazanfari, N; Ngo, S T; Gervásio, O L; Reddel, S W; Phillips, W D

    2010-09-01

    The postsynaptic muscle-specific kinase (MuSK) coordinates formation of the neuromuscular junction (NMJ) during embryonic development. Here we have studied the effects of MuSK autoantibodies upon the NMJ in adult mice. Daily injections of IgG from four MuSK autoantibody-positive myasthenia gravis patients (MuSK IgG; 45 mg day(1)i.p. for 14 days) caused reductions in postsynaptic ACh receptor (AChR) packing as assessed by fluorescence resonance energy transfer (FRET). IgG from the patients with the highest titres of MuSK autoantibodies caused large (51-73%) reductions in postsynaptic MuSK staining (cf. control mice; P < 0.01) and muscle weakness. Among mice injected for 14 days with control and MuSK patient IgGs, the residual level of MuSK correlated with the degree of impairment of postsynaptic AChR packing. However, the loss of postsynaptic MuSK preceded this impairment of postsynaptic AChR. When added to cultured C2 muscle cells the MuSK autoantibodies caused tyrosine phosphorylation of MuSK and the AChR beta-subunit, and internalization of MuSK from the plasma membrane. The results suggest a pathogenic mechanism in which MuSK autoantibodies rapidly deplete MuSK from the postsynaptic membrane leading to progressive dispersal of postsynaptic AChRs. Moreover, maintenance of postsynaptic AChR packing at the adult NMJ would appear to depend upon physical engagement of MuSK with the AChR scaffold, notwithstanding activation of the MuSK-rapsyn system of AChR clustering. PMID:20603331

  8. Precision medicine in myasthenia graves: begin from the data precision

    PubMed Central

    Hong, Yu; Xie, Yanchen; Hao, Hong-Jun; Sun, Ren-Cheng

    2016-01-01

    Myasthenia gravis (MG) is a prototypic autoimmune disease with overt clinical and immunological heterogeneity. The data of MG is far from individually precise now, partially due to the rarity and heterogeneity of this disease. In this review, we provide the basic insights of MG data precision, including onset age, presenting symptoms, generalization, thymus status, pathogenic autoantibodies, muscle involvement, severity and response to treatment based on references and our previous studies. Subgroups and quantitative traits of MG are discussed in the sense of data precision. The role of disease registries and scientific bases of precise analysis are also discussed to ensure better collection and analysis of MG data. PMID:27127759

  9. Slow-binding inhibition of acetylcholinesterase by an alkylammonium derivative of 6-methyluracil: mechanism and possible advantages for myasthenia gravis treatment.

    PubMed

    Kharlamova, Alexandra D; Lushchekina, Sofya V; Petrov, Konstantin A; Kots, Ekaterina D; Nachon, Florian; Villard-Wandhammer, Marielle; Zueva, Irina V; Krejci, Eric; Reznik, Vladimir S; Zobov, Vladimir V; Nikolsky, Evgeny E; Masson, Patrick

    2016-05-01

    Inhibition of human AChE (acetylcholinesterase) and BChE (butyrylcholinesterase) by an alkylammonium derivative of 6-methyluracil, C-547, a potential drug for the treatment of MG (myasthenia gravis) was studied. Kinetic analysis of AChE inhibition showed that C-547 is a slow-binding inhibitor of type B, i.e. after formation of the initial enzyme·inhibitor complex (Ki=140 pM), an induced-fit step allows establishment of the final complex (Ki*=22 pM). The estimated koff is low, 0.05 min(-1) On the other hand, reversible inhibition of human BChE is a fast-binding process of mixed-type (Ki=1.77 μM; Ki'=3.17 μM). The crystal structure of mouse AChE complexed with C-547 was solved at 3.13 Å resolution. The complex is stabilized by cation-π, stacking and hydrogen-bonding interactions. Molecular dynamics simulations of the binding/dissociation processes of C-547 and C-35 (a non-charged analogue) to mouse and human AChEs were performed. Molecular modelling on mouse and human AChE showed that the slow step results from an enzyme conformational change that allows C-547 to cross the bottleneck in the active-site gorge, followed by formation of tight complex, as observed in the crystal structure. In contrast, the related non-charged compound C-35 is not a slow-binding inhibitor. It does not cross the bottleneck because it is not sensitive to the electrostatic driving force to reach the bottom of the gorge. Thus C-547 is one of the most potent and selective reversible inhibitors of AChE with a long residence time, τ=20 min, longer than for other reversible inhibitors used in the treatment of MG. This makes C-547 a promising drug for the treatment of this disease. PMID:26929400

  10. Expression of a highly antigenic and native-like folded extracellular domain of the human α1 subunit of muscle nicotinic acetylcholine receptor, suitable for use in antigen specific therapies for Myasthenia Gravis.

    PubMed

    Niarchos, Athanasios; Zouridakis, Marios; Douris, Vassilis; Georgostathi, Assimina; Kalamida, Dimitra; Sotiriadis, Alexandros; Poulas, Konstantinos; Iatrou, Kostas; Tzartos, Socrates J

    2013-01-01

    We describe the expression of the extracellular domain of the human α1 nicotinic acetylcholine receptor (nAChR) in lepidopteran insect cells (i-α1-ECD) and its suitability for use in antigen-specific therapies for Myasthenia Gravis (MG). Compared to the previously expressed protein in P. pastoris (y-α1-ECD), i-α1-ECD had a 2-fold increased expression yield, bound anti-nAChR monoclonal antibodies and autoantibodies from MG patients two to several-fold more efficiently and resulted in a secondary structure closer to that of the crystal structure of mouse α1-ECD. Our results indicate that i-α1-ECD is an improved protein for use in antigen-specific MG therapeutic strategies. PMID:24376846

  11. Clinical aspects of myasthenia explained.

    PubMed

    Verschuuren, Jan J G M; Palace, Jackie; Gilhus, Nils Erik

    2010-08-01

    Myasthenia gravis and myasthenic syndromes are diseases of the neuromuscular junction. Autoantibodies and toxins to or mutations in one of the synaptic proteins are the main causes of dysfunction. Myasthenic phenotypes can be classified according to the basic aetiological mechanisms or divided depending on the clinical phenotype. PMID:20380587

  12. Genetics Home Reference: myasthenia gravis

    MedlinePlus

    ... AChR); in others, the antibodies attack a related protein called muscle-specific kinase (MuSK). In both cases, the abnormal antibodies lead to a reduction of available AChR. The AChR protein is critical for signaling between nerve and muscle ...

  13. Myasthenia Gravis (MG): Medical Management

    MedlinePlus

    ... for use only when other drugs fail. Myasthenic crisis Especially in people with bulbar or respiratory symptoms, ... can sometimes worsen to the point of myasthenic crisis , an extreme episode of weakness that culminates in ...

  14. Decreased microRNA miR-181c expression in peripheral blood mononuclear cells correlates with elevated serum levels of IL-7 and IL-17 in patients with myasthenia gravis.

    PubMed

    Zhang, Yong; Guo, Mingfeng; Xin, Ning; Shao, Zhen; Zhang, Xiuying; Zhang, Yanyan; Chen, Jing; Zheng, Shuangshuang; Fu, Linlin; Wang, YuZhong; Zhou, Dongmei; Chen, Hao; Huang, Yan; Dong, Ruiguo; Xiao, Chenghua; Liu, Yonghai; Geng, Deqin

    2016-08-01

    miR-181c is a newly identified negative regulator of immune cell activation. In this study, we aimed to investigate the expression and functional role of miR-181c in myasthenia gravis (MG). miR-181c showed significant downregulation in peripheral blood mononuclear cells (PBMCs) from MG patients compared with healthy controls, with lower expression in generalized patients than in ocular ones. MG patients also had increased serum IL-7 and IL-17 levels. Additionally, serum IL-7 level presents a positive correlation with the serum IL-17 level. miR-181c levels were negatively correlated with serum levels of IL-7 and IL-17 in either generalized patients or ocular patients. A luciferase reporter assay revealed that miR-181c could directly bind to the 3'-UTR of interleukin-7. Forced expression of miR-181c led to decreased IL-7 and IL-17 release in cultured PBMCs, while depletion of miR-181c increased the secretion of these two proinflammatory cytokines. The results from our study suggested for the first time that miR-181c was able to negatively regulate the production of proinflammatory cytokines IL-7 and IL-17 in MG patients, and it is a novel potential therapeutic target for MG. PMID:25962782

  15. [Glycosylation of autoantibodies in autoimmunes diseases].

    PubMed

    Goulabchand, R; Batteux, F; Guilpain, P

    2013-12-01

    Protein glycosylation is one of the most common post-translational modifications, involved in the well described protein biosynthesis process. Protein glycosylation seems to play a major role in the pathogenesis of auto-immune diseases. Herein are described the main alterations of autoantibody glycosylation associated with autoimmunes diseases such as rheumatoid arthritis, IgA glomerulonephritis, Schoenlein-Henoch purpura, Sjögren's syndrome, systemic scleroderma, systemic lupus erythematosus, myasthenia gravis and granulomatosis with polyangiitis (Wegener). Molecular identification of altered immunoglobulin glycosylation could lead to a better understanding of the pathogenesis of those diseases, might allow an evaluation of their biological activity and could even be a new therapeutic target. PMID:24139501

  16. Population Based Study of 12 Autoimmune Diseases in Sardinia, Italy: Prevalence and Comorbidity

    PubMed Central

    Sardu, Claudia; Cocco, Eleonora; Mereu, Alessandra; Massa, Roberta; Cuccu, Alessandro; Marrosu, Maria Giovanna; Contu, Paolo

    2012-01-01

    Background The limited availability of prevalence data based on a representative sample of the general population, and the limited number of diseases considered in studies about co-morbidity are the critical factors in study of autoimmune diseases. This paper describes the prevalence of 12 autoimmune diseases in a representative sample of the general population in the South of Sardinia, Italy, and tests the hypothesis of an overall association among these diseases. Methods Data were obtained from 21 GPs. The sample included 25,885 people. Prevalence data were expressed with 95% Poisson C.I. The hypothesis of an overall association between autoimmune diseases was tested by evaluating the co-occurrence within individuals. Results Prevalence per 100,000 are: 552 rheumatoid arthritis, 124 ulcerative colitis, 15 Crohn's disease, 464 type 1 diabetes, 81 systemic lupus erythematosus, 124 celiac disease, 35 myasthenia gravis, 939 psoriasis/psoriatic arthritis, 35 systemic sclerosis, 224 multiple sclerosis, 31 Sjogren's syndrome, and 2,619 autoimmune thyroiditis . An overall association between autoimmune disorders was highlighted. Conclusions The comparisons with prevalence reported in current literature do not show outlier values, except possibly for a few diseases like celiac disease and myasthenia gravis. People already affected by a first autoimmune disease have a higher probability of being affected by a second autoimmune disorder. In the present study, the sample size, together with the low overall prevalence of autoimmune diseases in the population, did not allow us to examine which diseases are most frequently associated with other autoimmune diseases. However, this paper makes available an adequate control population for future clinical studies aimed at exploring the co-morbidity of specific pairs of autoimmune diseases. PMID:22396771

  17. [Directions for use of corticosteroids and calcineurin inhibitors against generalized myasthenia gravis: therapeutic strategies that can lead to early improvements and veer away from high-dose oral corticosteroids].

    PubMed

    Utsugisawa, Kimiaki; Nagane, Yuriko; Suzuki, Shigeaki; Suzuki, Norihiro

    2012-01-01

    The advent of effective immune treatment has meant that myasthenia gravis (MG) is most often not lethal. However, many MG patients still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of medication, since full remission without immune treatment is not common. Our analysis demonstrated that disease severity, dose of oral corticosteroids, and depressive state are the major independent factors negatively associated with self-reported QOL (MG-QOL15-J score). It is noteworthy that oral corticosteroid, the first-line agent for MG, is negatively associated with patients' QOL. When the analysis took into account MGFA postintervention status and dose of oral prednisolne (PSL), the MG-QOL15-J score of MM status patients taking ≤ 5 mg PSL per day is identically low (i.e., just as good QOL) as that seen in CSR and is a target of treatment. In order to veer away from high-dose oral corticosteroids and to achieve early MM or better status with PSL ≤ 5 mg/day, we advocate the early aggressive treatment strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved clinical status using low-dose oral corticosteroids and calcineurin inhibitors (cyclosporine microemulsion and tacrolimus). The early stages of MG are susceptible to treatment with calcineurin inhibitors. When using cyclosporine microemulsion for MG, blood concentrations 2 h after administration (C2) correlate with clinical improvement and immediately before administration (C0) with side effects (increased serum creatinine and/or hypertension). Monitoring of C2 and C0 levels is useful to estimate efficacy and safety of the drug. PMID:23196511

  18. [Diagnostics of autoimmune diseases].

    PubMed

    Beleznay, Zsuzsanna; Regenass, Stephan

    2008-09-01

    Autoantibodies play a key role in diagnostic laboratories as markers of autoimmune diseases. In addition to their role as markers they mediate diverse effects in vivo. Autoantibodies with protective effect have been described. Natural protective IgM autoantibodies against tumour-antigens of malignant cells or their precursors may contribute to increased survival rates of carcinoma patients. In a mouse model of systemic lupus erythematosus it has been shown that anti-dsDNA IgM autoantibodies protect from glomerular damage. In contrast, a direct pathogenic role of autoantibodies has been well established e.g. in myasthenia gravis or in Goodpasture syndrome. Similarly autoantibodies against SSA Ro52 are detrimental in neonatal lupus erythematosus with congenital heart block. Moreover, putatively protective autoantibodies may become pathogenic during the course of the disease such as the onconeuronal autoantibodies whose pathogenicity depends on their compartmentalisation. In patients with paraneoplastic syndromes tumour cells express proteins that are also naturally present in the brain. Anti-tumour autoantibodies which temporarily suppress tumour growth can provoke an autoimmune attack on neurons once having crossed the blood-brain barrier and cause specific neurological symptoms. Only a restricted number of autoantibodies are useful follow-up markers for the effectiveness of treatment in autoimmune diseases. Certain autoantibodies hold prognostic value and appear years or even decades before the diagnosis of disease such as the antimitochondrial antibodies in primary biliary cirrhosis or anti-citrullinated protein (CCP)-antibodies in rheumatoid arthritis. It is crucial to know whether the autoantibodies in question recognise linear or conformational epitopes in order to choose the appropriate detection methods. Indirect immunofluorescence microscopy remains a very useful tool for confirmation of results of commercially available immunoassays and for detection of

  19. Latent polyglandular autoimmune syndrome type 2 case diagnosed during a shock manifestation.

    PubMed

    Gürkan, Eren; Çetinarslan, Berrin; Güzelmansur, İsmail; Kocabaş, Beyza

    2016-07-01

    There are many types of polyglandular autoimmune syndrome (PAS). PAS type 2 is the most common type among adults. For PAS type 2 (PAS-2) diagnosis, detection of Addison's disease with autoimmune thyroid disease and/or type 1 diabetes mellitus are required. Premature ovarian insufficiency, pernicious anemia, vitiligo, alopecia, myasthenia gravis, celiac disease and autoimmune diabetes insipidus may be comorbidities of this condition. Contrary to the common belief, latent PAS is more common than the manifest forms. Here, we present a PAS-2 case diagnosed via adrenal crisis. At the time of diagnosis, the case was observed to have thyroid, adrenal and ovarian involvement. Therefore, PAS-2 and possible immunologic disorders were discussed. PMID:26806667

  20. A Difficult and Rare Diagnosis of Autoimmune Enteropathy in a Patient Affected by Down Syndrome.

    PubMed

    Depince-Berger, Anne; Cremilieux, Clara; Rinaudo-Gaujous, Melanie; Genin, Christian; de Freminville, Benedicte; Lambert, Claude; Bruneau, J; Paul, Stephane

    2016-07-01

    Patients with Down syndrome are more susceptible to autoimmune pathologies, in particular endocrine or digestive diseases such as celiac disease. Autoimmune enteropathy is another form of digestive autoimmune disease, non-gluten-dependant, more often diagnosed in male neonates with immunodysregulation and polyendocrinopathy such as the Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome. It also exists in the adult, but this pathology is less known and therefore frequently under-diagnosed. Clinical manifestations are similar to celiac disease, but not improved after a gluten-free diet. Autoimmune enteropathy is frequently associated with other autoimmune diseases, such as thyroiditis, myasthenia gravis, lupus or immune deficiencies, as Common Variable Immunodeficiency. Pathological analysis of intestinal biopsies can frequently distinguish autoimmune enteropathy and celiac disease. Autoimmune enteropathy usually has an important lymphoplasmacytic infiltration of the mucosa and a lack of intraepithelial lymphocytes in the gastrointestinal mucosal surface, while celiac disease usually has a polymorph infiltration of the mucosa and an important intraepithelial lymphocytes infiltration. Nevertheless, the two pathological patterns may overlap. Here we report the first case of a patient with Down syndrome associated to autoimmune enteropathy (initially diagnosed as celiac disease), chronic pancreatitis and cutaneous lupus erythematosus. Even if autoimmune pathologies are much more common in patients with Down syndrome, we would like to report on this rare and original association found in our patient. PMID:27072857

  1. [Acquired von Willebrand's disease in the course of severe primary hypothyroidism in a patient with autoimmune polyglandular syndrome type 3].

    PubMed

    Lubińska, Monika; Swiatkowska-Stodulska, Renata; Kazimierska, Ewa; Sworczak, Krzysztof

    2008-01-01

    The case of a 20-year old female, who had been followed because of von Willebrand disease (vWD) was presented in this paper . She had a past history of menorrhagia and bleeding after dental procedures and the activity of von Willebrand factor (vWF) was decreased. Because of suggestive clinical features, the workup for hypothyroidism was performed and the patient was found to have severe hypothyroidism due to Hashimoto thyroiditis. After the institution of replacement therapy with levothyroxine, von Willebrand factor activity returned to normal range and symptoms of von Willebrand disease disappeared. Based on these findings, the diagnosis of acquired von Willebrand syndrome (AvWS) due to hypothyroidism was made. The development of myasthenia led to the final diagnosis of autoimmune polyglandular syndrome type 3 (APS) with myasthenia gravis and vitiligo. PMID:18335399

  2. Myasthenia Gravis: Tests and Diagnostic Methods

    MedlinePlus

    ... Affiliations Foundation Focus Newsletter E-Update Test & Diagnostic methods In addition to a complete medical and neurological ... How can I help? About MGFA Test & Diagnostic methods Treatment for MG FAQ's Upcoming Events Spring 2016 ...

  3. An investigation of experimental myasthenia gravis

    PubMed Central

    Jones, S. F.; Brennan, J. L.; McLeod, J. G.

    1971-01-01

    Guinea-pigs were immunized with antigen prepared from calf thymus and muscle, and from guinea-pig thymus, and rats were immunized with antigen prepared from rat thymus and rat muscle. There was an increased incidence of delayed hypersensitivity and circulating thymus antibodies in the immunized guinea-pigs and an increased incidence of thymitis in the immunized guinea-pigs and rats. However, when compared with control animals, there was no electrophysiological evidence of impairment of neuromuscular transmission in the immunized animals. Images PMID:4328884

  4. Immune Globulin Intravenous: Myasthenia Gravis (Acute Exacerbation).

    PubMed

    Generali, Joyce A; Cada, Dennis J

    2015-10-01

    This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@ku.edu. PMID:26912917

  5. Myasthenia Gravis: Drugs to be Avoided

    MedlinePlus

    ... explanation) on this drug in MG patients. • The fluoroquinolones , including Ciprofloxacin and Levofloxacin – commonly prescribed antibiotics that ... drugs that carry black box warnings include the fluoroquinolones (e.g. Ciprofloxacin , Levafloxacin ; see above) and Telethromycin ( ...

  6. Myasthenia Crisis Induced by Pegylated-Interferon in Patient With Chronic Hepatitis C

    PubMed Central

    Baik, Su Jung; Kim, Tae Hun; Kim, Hye In; Rhie, Jeong Yeon

    2016-01-01

    Abstract Myasthenia gravis is occasionally associated with thymoma that needs surgical resection and may progress to severe respiratory failure. We experienced a rare case of myasthenia crisis during antiviral therapy for chronic hepatitis C, in whom mediastinal thymoma was discovered and successfully managed with surgical thymectomy and meticulous medical care. A 47-year-old-male patient complained of sudden diplopia 1 week after stopping 11-week administration of pegylated-interferon and ribavirin for chronic hepatitis C. Ophthalmologic examinations revealed ptosis on the right eyelid and restricted right eye movement. Myasthenia gravis was confirmed by positive repetitive nerve stimulation test and positive serum antiacetylcholine receptor antibody test, and mediastinal thymoma was found on chest CT scan. The ocular myasthenia gravis progressed to respiratory failure even after discontinuing antiviral treatment but eventually recovered with thymectomy, anticholinesterase administration, steroid pulse therapy, and prolonged ventilator care. We describe the clinical features of this life-threatening complication of interferon treatment along with previous myasthenia crisis cases by interferon for chronic hepatitis C. In patients with chronic hepatitis C who is going to receive interferon-based antiviral treatment, physicians need to keep in mind the potential life-threatening manifestations of myasthenia gravis before and during antiviral treatment especially when patients complain of muscular weakness and easy fatigability. PMID:27227948

  7. Myasthenia Crisis Induced by Pegylated-Interferon in Patient With Chronic Hepatitis C: A Case Report.

    PubMed

    Baik, Su Jung; Kim, Tae Hun; Kim, Hye In; Rhie, Jeong Yeon

    2016-05-01

    Myasthenia gravis is occasionally associated with thymoma that needs surgical resection and may progress to severe respiratory failure. We experienced a rare case of myasthenia crisis during antiviral therapy for chronic hepatitis C, in whom mediastinal thymoma was discovered and successfully managed with surgical thymectomy and meticulous medical care.A 47-year-old-male patient complained of sudden diplopia 1 week after stopping 11-week administration of pegylated-interferon and ribavirin for chronic hepatitis C. Ophthalmologic examinations revealed ptosis on the right eyelid and restricted right eye movement. Myasthenia gravis was confirmed by positive repetitive nerve stimulation test and positive serum antiacetylcholine receptor antibody test, and mediastinal thymoma was found on chest CT scan. The ocular myasthenia gravis progressed to respiratory failure even after discontinuing antiviral treatment but eventually recovered with thymectomy, anticholinesterase administration, steroid pulse therapy, and prolonged ventilator care. We describe the clinical features of this life-threatening complication of interferon treatment along with previous myasthenia crisis cases by interferon for chronic hepatitis C.In patients with chronic hepatitis C who is going to receive interferon-based antiviral treatment, physicians need to keep in mind the potential life-threatening manifestations of myasthenia gravis before and during antiviral treatment especially when patients complain of muscular weakness and easy fatigability. PMID:27227948

  8. Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party.

    PubMed

    Daikeler, Thomas; Labopin, Myriam; Di Gioia, Massimo; Abinun, Mario; Alexander, Tobias; Miniati, Irene; Gualandi, Francesca; Fassas, Athanasios; Martin, Thierry; Schwarze, Carl Philipp; Wulffraat, Nico; Buch, Maya; Sampol, Antonia; Carreras, Enric; Dubois, Benedicte; Gruhn, Bernd; Güngör, Tayfun; Pohlreich, David; Schuerwegh, Annemie; Snarski, Emilian; Snowden, John; Veys, Paul; Fasth, Anders; Lenhoff, Stig; Messina, Chiara; Voswinkel, Jan; Badoglio, Manuela; Henes, Jörg; Launay, David; Tyndall, Alan; Gluckman, Eliane; Farge, Dominique

    2011-08-11

    To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34(+) graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT. PMID:21596847

  9. Myasthenia and related disorders of the neuromuscular junction.

    PubMed

    Spillane, Jennifer; Beeson, David J; Kullmann, Dimitri M

    2010-08-01

    Our understanding of transmission at the neuromuscular junction has increased greatly in recent years. We now recognise a wide variety of autoimmune and genetic diseases that affect this specialised synapse, causing muscle weakness and fatigue. These disorders greatly affect quality of life and rarely can be fatal. Myasthenia gravis is the most common disorder and is most commonly caused by autoantibodies targeting postsynaptic acetylcholine receptors. Antibodies to muscle-specific kinase (MuSK) are detected in a variable proportion of the remainder. Treatment is symptomatic and immunomodulatory. Lambert-Eaton myasthenic syndrome is caused by antibodies to presynaptic calcium channels, and approximately 50% of cases are paraneoplastic, most often related to small cell carcinoma of the lung. Botulism is an acquired disorder caused by neurotoxins produced by Clostridium botulinum, impairing acetylcholine release into the synaptic cleft. In addition, several rare congenital myasthenic syndromes have been identified, caused by inherited defects in presynaptic, synaptic basal lamina and postsynaptic proteins necessary for neuromuscular transmission. This review focuses on recent advances in the diagnosis and treatment of these disorders. PMID:20547629

  10. [Intravenous immunoglobulin in treatment of autoimmune neurological diseases in children].

    PubMed

    Bembeeva, R Ts; Zavadenko, N N

    2015-01-01

    Though the mechanisms of action of intravenous immunoglobulins (IVIG) are not completely understood, these drugs are widely used in treatment of autoimmune diseases. In this review, we have analyzed the literature on the use of IVIG in the treatment of autoimmune diseases of the nervous system in children and discuss the management of patients basing on the recommendation of the European Federation of Neurological Societies. The efficacy of IVIG in children has been shown as first line treatment in Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, dermatomyositis as a second-line drug in the combination with prednisolone or immunosuppressors in patients refractory to treatment with corticosteroids and cytostatics, myasthenic crisis in myasthenia gravis, exacerbations and short-term treatment of severe forms, non-responsiveness to acetylcholinesterase inhibitors, multiple sclerosis as second or third line of treatment in patients with relapsing-remitting course with intolerance to standard immunomodulatory therapy, acute multiple encephalomyelitis with no response to the treatment with high doses of corticosteroids, paraneoplastic syndromes, pharmacoresistant epilepsy and autoimmune encephalitis. Because the right choice of the drug plays a key role, in particular, in children, that determines the efficacy and safety of the treatment, we present the main approaches to the choice of the drug and schemes of treatment of autoimmune diseases of the nervous system in children. PMID:26356621

  11. Current and future immunotherapy targets in autoimmune neurology.

    PubMed

    Hu, Melody Y; Stathopoulos, Panos; O'connor, Kevin C; Pittock, Sean J; Nowak, Richard J

    2016-01-01

    Randomized controlled treatment trials of autoimmune neurologic disorders are generally lacking and data pertaining to treatment are mostly derived from expert opinion, large case series, and anecdotal reports. The treatment of autoimmune neurologic disorders comprises oncologic therapy (where appropriate) and immunotherapy. In this chapter, we first describe the standard acute and chronic immunotherapies and provide a practical overview of their use in the clinic (mechanisms of action, dosing, monitoring, and side effects). Novel approaches to treatment of autoimmune neurologic disorders, through new drug discovery or repurposing, are dependent on improved mechanistic understanding of immunopathology. Such approaches, with emphasis on monoclonal antibodies, are discussed using the paradigm of three autoimmune neurologic disorders whose immunopathogenesis is better understood, specifically myasthenia gravis, neuromyelitis optica, and chronic inflammatory demyelinating polyradiculoneuropathy. It is important to realize that the treatment strategy and management plan must be individualized for each patient. In general these are influenced by the following: clinical severity, antibody type, presence or absence of cancer, and prior treatment response, if known. PMID:27112694

  12. Animal models of antimuscle specific kinase myasthenia

    PubMed Central

    Richman, David P.; Nishi, Kayoko; Ferns, Michael J.; Schnier, Joachim; Pytel, Peter; Maselli, Ricardo A.; Agius, Mark A.

    2014-01-01

    Antimuscle specific kinase (anti-MuSK) myasthenia (AMM) differs from antiacetylcholine receptor myasthenia gravis in exhibiting more focal muscle involvement (neck, shoulder, facial, and bulbar muscles) with wasting of the involved, primarily axial, muscles. AMM is not associated with thymic hyperplasia and responds poorly to anticholinesterase treatment. Animal models of AMM have been induced in rabbits, mice, and rats by immunization with purified xenogeneic MuSK ectodomain, and by passive transfer of large quantities of purified serum IgG from AMM patients into mice. The models have confirmed the pathogenic role of the MuSK antibodies in AMM and have demonstrated the involvement of both the presynaptic and postsynaptic components of the neuromuscular junction. The observations in this human disease and its animal models demonstrate the role of MuSK not only in the formation of this synapse but also in its maintenance. PMID:23252909

  13. Hypothetical review: thymic aberrations and type-I interferons; attempts to deduce autoimmunizing mechanisms from unexpected clues in monogenic and paraneoplastic syndromes.

    PubMed

    Meager, A; Peterson, P; Willcox, N

    2008-10-01

    In sporadic autoimmune disorders, dendritic cells are increasingly being incriminated as agents provocateurs. However, the mechanisms and any 'danger signals' that induce them to autoimmunize remain enigmatic. Here, we focus on unexpected clues from two prototypic/ highly informative autoimmune syndromes, acquired thymoma-associated myasthenia gravis and the monogenic autoimmune polyendocrine syndrome type-1 (APS1), caused by mutations in the AutoImmune Regulator (AIRE). Both involve the thymus, and in both we find early, persistent, highly prevalent and high-titre neutralizing autoantibodies against type-I interferons, regardless of the exact AIRE genotype or the characteristically variable clinical phenotype in APS1. Thus these key innate<-->adaptive immune intermediaries are now implicated in APS1 and paraneoplastic myasthenia as well as in systemic lupus erythematosus and other sporadic autoimmune disorders. The currently accepted notion that autoimmunization proceeds automatically (by 'default') does not explain how, when or where autoimmune responses are initiated against which targets in APS1, or whether exogenous or internal danger signals are involved, or predict whether the primary auto-immunogenic targets are AIRE-dependent. As the parallels between these syndromes must hold novel clues to these puzzles, they demand explanations. To unify these and other findings, we propose that autoimmunization occurs centrally in aberrant thymic environments rendered 'dangerous' by AIRE-deficiency (possibly by excess undegraded nucleic acids/dead cell debris). The ensuing autoreactivity focuses early on the locally abundant type I interferons and then on other peripheral tissue autoantigens that are still expressed despite the absence of AIRE. These ideas raise numerous questions that others may already have the materials to address. PMID:18727623

  14. MuSK Myasthenia Gravis IgG4 Disrupts the Interaction of LRP4 with MuSK but Both IgG4 and IgG1-3 Can Disperse Preformed Agrin-Independent AChR Clusters

    PubMed Central

    Koneczny, Inga; Cossins, Judith; Waters, Patrick; Beeson, David; Vincent, Angela

    2013-01-01

    A variable proportion of patients with generalized myasthenia gravis (MG) have autoantibodies to muscle specific tyrosine kinase (MuSK). During development agrin, released from the motor nerve, interacts with low density lipoprotein receptor-related protein-4 (LRP4), which then binds to MuSK; MuSK interaction with the intracellular protein Dok7 results in clustering of the acetylcholine receptors (AChRs) on the postsynaptic membrane. In mature muscle, MuSK helps maintain the high density of AChRs at the neuromuscular junction. MuSK antibodies are mainly IgG4 subclass, which does not activate complement and can be monovalent, thus it is not clear how the antibodies cause disruption of AChR numbers or function to cause MG. We hypothesised that MuSK antibodies either reduce surface MuSK expression and/or inhibit the interaction with LRP4. We prepared MuSK IgG, monovalent Fab fragments, IgG1-3 and IgG4 fractions from MuSK-MG plasmas. We asked whether the antibodies caused endocytosis of MuSK in MuSK-transfected cells or if they inhibited binding of LRP4 to MuSK in co-immunoprecipitation experiments. In parallel, we investigated their ability to reduce AChR clusters in C2C12 myotubes induced by a) agrin, reflecting neuromuscular development, and b) by Dok7- overexpression, producing AChR clusters that more closely resemble the adult neuromuscular synapse. Total IgG, IgG4 or IgG1-3 MuSK antibodies were not endocytosed unless cross-linked by divalent anti-human IgG. MuSK IgG, Fab fragments and IgG4 inhibited the binding of LRP4 to MuSK and reduced agrin-induced AChR clustering in C2C12 cells. By contrast, IgG1-3 antibodies did not inhibit LRP4-MuSK binding but, surprisingly, did inhibit agrin-induced clustering. Moreover, both IgG4 and IgG1-3 preparations dispersed agrin-independent AChR clusters in Dok7-overexpressing C2C12 cells. Thus interference by IgG4 antibodies of the LRP4-MuSK interaction will be one pathogenic mechanism of MuSK antibodies, but IgG1-3 Mu

  15. Vitiligo vulgaris and autoimmune diseases in Japan: A report from vitiligo clinic in Kyoto University Hospital.

    PubMed

    Tanioka, Miki; Yamamoto, Yosuke; Katoh, Mayumi; Takahashi, Kenzo; Miyachi, Yoshiki

    2009-01-01

    We reviewed the causes of "loss of skin color" in 144 patients, who visited Vitiligo Clinic of Kyoto University Hospital between April 2005 and August 2008. The numbers of patients with generalized and segmental Vitiligo vulgaris were 98 (68.1%) and 26 (18.1%), respectively. Small numbers of the patients suffered from Vogt-Koyanagi-Harada disease, piebaldism, congenital albinism, Hypomelanosis of Ito, post-inflammatory hypopigmentation, white leaf-shaped macules associated with tuberous sclerosis and nevus hypopigmentosus. One forth of the patients with generalized vitiligo had complications, while no complications were found in the patients with segmental vitiligo. Among the complications, autoimmune diseases dominated 43% (10 of 23 cases). Autoimmune thyroid diseases explained for the most of the complicated autoimmune diseases and were associated with 7.4% of the patients with generalized vitiligo. Minor autoimmune complications include myasthenia gravis, Sjogren syndrome and autoimmune nephritis. Reflecting the condition that our clinic is located in a university hospital, vitiligo patients with end-stage non-melanoma cancers of internal organs accounted for 8.4% of the patients of generalized vitiligo. PMID:20046588

  16. Targeting FcγRs to treat antibody-dependent autoimmunity.

    PubMed

    Yu, Xiaojie; Lazarus, Alan H

    2016-06-01

    Self-reactive antibodies represent a significant force in autoimmune disease induction. In antibody-dependent autoimmune syndromes such as immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE), myasthenia gravis and rheumatoid arthritis (RA), autoantibodies exert their inflammatory effect through FcγRs, a well-established class of cell surface receptors that interact with the Fc domain of IgG. Down-regulating FcγR functionality presents an attractive strategy to treat antibody-dependent autoimmune diseases. Various approaches, including nonspecific blocking of the IgG binding site as well as specific targeting using antagonistic monoclonal antibodies, have been explored to modulate the interaction between the Fc portion of IgG and FcγRs. The exquisite specificity and favorable pharmacokinetics of IgG make monoclonal antibodies a preferred choice. Indeed, the first antagonistic monoclonal antibody against the human FcγRIIIA had shown efficacy in refractory ITP patients; however, the practicality of using anti-FcγRIII antibody as a therapeutic was hindered by its associated adverse events, a phenomenon recapitulated in animal models. In this review, we discuss the role of FcγRs in autoimmune diseases, and focus on a novel monovalent approach to target FcγRs to resolve antibody-mediated autoimmunity. PMID:26854400

  17. Practical considerations on the use of rituximab in autoimmune neurological disorders

    PubMed Central

    Kosmidis, Mixalis L.; Dalakas, Marinos C.

    2010-01-01

    Rituximab (Mabthera, Rituxan) is a chimeric human/murine monoclonal antibody against CD-20 surface antigen expressed on B-cells. Rituximab, by causing B-cell depletion, appears to be effective in several autoimmune disorders; it has been approved for rheumatoid arthritis and is a promising new agent in the treatment of several autoimmune neurological disorders. A controlled study in patients with relapsing remitting multiple sclerosis has shown that rituximab significantly reduces the number of new MRI lesions and improves clinical outcome; it also showed some promise in a subset of patients with primary progressive MS. The drug is also effective in a number of patients with Devic’s disease, myasthenia gravis, autoimmune neuropathies, and inflammatory myopathies. The apparent effectiveness of rituximab has moved B-cells into the center stage of clinical and laboratory investigation of autoimmune neurological disorders. We review the evidence-based effectiveness of rituximab in neurological disorders based on controlled trials and anecdotal reports, including our own experience, and address the immunobiology of B-cells in autoimmune central nervous system (CNS) and peripheral nervous system (PNS) disorders. In addition, we provide practical guidelines on how best to use this drug in clinical practice and highlight its potential toxicity. PMID:21179602

  18. Therapeutic gymnastics in comprehensive treatment of patients with generalized myasthenia

    NASA Technical Reports Server (NTRS)

    Kapelovich, R. L.

    1980-01-01

    The technique of therapeutic gymnastics was used for patients with mayasthenia gravis to control the consequences of hypodynamia induced by the myasthenic process. It is concluded that during myasthenia, the severity of the disease is due to the affection of the cross striated musculature. The most life threatening are the disorders in respiration and swallowing, that can be intensified by forced stay in bed and immobility. It is also concluded that the use of therapeutic gymnastics in patients which myasthenia promotes efficient presurgical preparation, and in the post surgical period; prevention of pulmonary complications and normalization of respiration. Therapeutic gymnastics with regard to the severity and localization of the myasthenic disorders must be a component part of the presurgical preparation and postsurgical management of patients with generalized myasthenia.

  19. Cumulative Childhood Stress and Autoimmune Diseases in Adults

    PubMed Central

    Dube, Shanta R.; Fairweather, DeLisa; Pearson, William S.; Felitti, Vincent J.; Anda, Robert F.; Croft, Janet B.

    2012-01-01

    Objective To examine whether childhood traumatic stress increased the risk of developing autoimmune diseases as an adult. Methods Retrospective cohort study of 15,357 adult health maintenance organization members enrolled in the Adverse Childhood Experiences (ACEs) Study from 1995 to 1997 in San Diego, California, and eligible for follow-up through 2005. ACEs included childhood physical, emotional, or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental divorce, and/or an incarcerated household member. The total number of ACEs (ACE Score range = 0–8) was used as a measure of cumulative childhood stress. The outcome was hospitalizations for any of 21 selected autoimmune diseases and 4 immunopathology groupings: T- helper 1 (Th1) (e.g., idiopathic myocarditis); T-helper 2 (Th2) (e.g., myasthenia gravis); Th2 rheumatic (e.g., rheumatoid arthritis); and mixed Th1/Th2 (e.g., autoimmune hemolytic anemia). Results Sixty-four percent reported at least one ACE. The event rate (per 10,000 person-years) for a first hospitalization with any autoimmune disease was 31.4 in women and 34.4 in men. First hospitalizations for any autoimmune disease increased with increasing number of ACEs (p < .05). Compared with persons with no ACEs, persons with ≥2 ACEs were at a 70% increased risk for hospitalizations with Th1, 80% increased risk for Th2, and 100% increased risk for rheumatic diseases (p < .05). Conclusions Childhood traumatic stress increased the likelihood of hospitalization with a diagnosed autoimmune disease decades into adulthood. These findings are consistent with recent biological studies on the impact of early life stress on subsequent inflammatory responses. PMID:19188532

  20. Immunomodulatory vaccines against autoimmune diseases.

    PubMed

    Sela, Michael

    2006-01-01

    Vaccines are for healthy people, to prevent them from becoming ill. Such prophylactic vaccines have been a great success. Therapeutic vaccines become more and more important, especially as life expectancy increases. Efforts to develop vaccines against such diseases as cancer, AIDS, hepatitis, tuberculosis, Alzheimer disease, and mad cow disease have not yet reached the stage where they can be successfully used on a daily basis. However, significant progress has been made in the realm of autoimmune diseases, resulting (at least in one case) in an immunomodulatory vaccine against multiple sclerosis that was developed in the author's laboratory, and that is in daily use by about 100,000 patients. The drug or therapeutic vaccine against the exacerbating-remitting type of multiple sclerosis is a copolymer of four amino acid residues, denoted Copaxone, which are related to myelin basic protein. This paper discusses Copaxone as well as a candidate immunomodulatory vaccine against myasthenia gravis, a peptide derived from the nicotinic acetylcholine receptor. Copolymer 1 (Cop 1, glatiramer acetate, Copaxone) is a synthetic amino acid random copolymer that is immunologically cross-reactive with myelin basic protein and suppresses experimental allergic encephalomyelitis in several animal species. Cop 1 slows the progression of disability and reduces the relapse rate in exacerbating-remitting multiple sclerosis patients. Cop 1 is a potent inducer of T helper 2 (Th2) regulatory cells in mice and humans; and Th2 cells are found in both the brains and spinal cords of Cop 1-treated mice and humans. MG and experimental autoimmune MG are T cell-regulated, antibody-mediated autoimmune diseases. Two peptides, representing sequences of the human AChR-alpha-subunit, p195-212 and p259-271, are immunodominant T-cell epitopes in MG patients and two strains of mice. Altered peptide ligand, composed of the randomly arranged two single amino acid analogs inhibits in vitro and in vivo MG

  1. Characterization of the in vitro expressed autoimmune rippling muscle disease immunogenic domain of human titin encoded by TTN exons 248-249

    SciTech Connect

    Zelinka, L.; McCann, S.; Budde, J.; Sethi, S.; Guidos, M.; Giles, R.; Walker, G.R.

    2011-08-05

    Highlights: {yields} Affinity purification of the autoimmune rippling muscle disease immunogenic domain of titin. {yields} Partial sequence analysis confirms that the peptides is in the I band region of titin. {yields} This region of the human titin shows high degree of homology to mouse titin N2-A. -- Abstract: Autoimmune rippling muscle disease (ARMD) is an autoimmune neuromuscular disease associated with myasthenia gravis (MG). Past studies in our laboratory recognized a very high molecular weight skeletal muscle protein antigen identified by ARMD patient antisera as the titin isoform. These past studies used antisera from ARMD and MG patients as probes to screen a human skeletal muscle cDNA library and several pBluescript clones revealed supporting expression of immunoreactive peptides. This study characterizes the products of subcloning the titin immunoreactive domain into pGEX-3X and the subsequent fusion protein. Sequence analysis of the fusion gene indicates the cloned titin domain (GenBank ID: (EU428784)) is in frame and is derived from a sequence of N2-A spanning the exons 248-250 an area that encodes the fibronectin III domain. PCR and EcoR1 restriction mapping studies have demonstrated that the inserted cDNA is of a size that is predicted by bioinformatics analysis of the subclone. Expression of the fusion protein result in the isolation of a polypeptide of 52 kDa consistent with the predicted inferred amino acid sequence. Immunoblot experiments of the fusion protein, using rippling muscle/myasthenia gravis antisera, demonstrate that only the titin domain is immunoreactive.

  2. Association of a wide invasive malignant thymoma with myastenia gravis and primary hyperparathyroidism due to parathyroid adenoma: case report and review of the literature.

    PubMed

    Triggiani, Vincenzo; Guastamacchia, Edoardo; Lolli, Ivan; Troccoli, Giuseppe; Resta, Francesco; Sabbà, Carlo; Ruggieri, Nadia; Tafaro, Emilio

    2006-01-01

    There are few cases described in the world literature reporting an association of thymoma (with myasthenia gravis or not) with hyperparathyroidism. In these cases the hyperparathyroidism was due to the presence of an adenoma or hyperplasic parathyroid tissue either in the cervical region or in an ectopic intrathymic location.(12345) In other cases the syndrome of hypercalcemia was due to the secretion of parathyroid-related protein (PTHRP) (6) or parathyroid hormone (PTH) (7) by the thymoma itself. We report the first case, at the best of our knowledge, of a wide invasive malignant thymoma (type B3), associated with myasthenia gravis and hyperparathyroidism caused by parathyroid adenoma. PMID:16873103

  3. Mannose-binding Lectin Mediated Complement Pathway in Autoimmune Neurological Disorders.

    PubMed

    Farrokhi, Mehrdad; Dabirzadeh, Mehrnoosh; Dastravan, Nastaran; Etemadifar, Masoud; Ghadimi, Keyvan; Saadatpour, Zahra; Rezaei, Ali

    2016-06-01

    Multiple sclerosis (MS) is a complex, demyelinating disease of the central nervous system (CNS) with variable phenotypic presentations, while Guillain-Barre Syndrome (GBS) is the prototypic acute inflammatory disorder that affects the peripheral nervous system. Myasthenia gravis (MG) is a T cell dependent and antibody mediated autoimmune disease. Although it has been shown that complement plays a critical role in the pathogenesis of MS, GBS, and MG, the role of mannose-binding lectin (MBL) as a biomarker of immunopathogensis of these diseases and also its association with the severity of them have been poorly investigated. Therefore, in this study we aimed to measure plasma levels of MBL in patients with MS, GBS, and MG. In a case-control study, plasma was obtained from healthy controls (n=100) and also patients with MS (n=120), GBS (n=30), and MG (n=30). Plasma level measurement of MBL was performed using enzyme-linked immunosorbent assay (ELISA). The mean serum level of MBL was significantly different between groups of patients and healthy controls (p<0.001). We also found a positive correlation between plasma levels of MBL and severity scores of MS, MG, and GBS patients including: expanded disability status scale (EDSS) (r=+0.60 and p=<0.001), quantitative myasthenia gravis score (QMGS) (r=+0.56 and p=0.01), and GBS disability scale (GDS) (r=+0.37 and p=0.04). Taken together, our findings suggest that complement activation mediated by MBL contributes to the pathogenesis and also severity of MS, MG, and GBS. However, because the lectin pathway can be involved in several phases of the immune response, further evidence will be required to elucidate the underlying mechanism. PMID:27424141

  4. P15: The expression of Tc17 cells in thymoma accompany with autoimmune diseases or autoimmune disorders

    PubMed Central

    Zhang, Peng

    2015-01-01

    Background Thymoma is thymic epithelial cell tumor. Studies have shown that thymoma associated with autoimmune disorders and possible mechanisms of autoimmune diseases is the central immune tolerance and peripheral tolerance obstacles have resulted in the breaking of the autoimmune response activation and immune tolerance. Tc17 cells and Th17 cells have been shown play an important role in tumor and autoimmune diseases’ development process. This study test the distribution of Tc17cells in thymoma and the expression of RORγt in thymus of thymoma patients with myasthenia gravis (MG) or other autoimmune diseases, the frequency of Th17/Tc17 in PBMCs, to explore the expression of Th17/Tc17 cells in thymoma accompany with autoimmune diseases or autoimmune disorders. Methods In this study, grouped as follows: (I) thymoma non gravis group (Tm groups); (II) thymoma with MG group thymoma with MG (MG group); (III) thymoma with MG associated with other autoimmune diseases group or anti- nuclear antibodies abnormal elevation of the group (AD group), to analyze the basic differences between the groups. In this study, we examined the RT-PCR to detect RORγt in the thymoma tissue, immunohistochemical double staining method to detect Tc17 cells expression and localization in the thymoma tissue distribution expression Th17/Tc17 in PBMCs by flow cytometry [Interleukin (IL)-17-producing CD8+ cells as Thl7 cells and IL-17-producing CD4+ cells as Tcl7 cells], analysis of differential expression of three in each group thymoma; and explore of Th17/Tc17 expression. Results (I) Tm groups and AD group serum CD8+ cells was statistically significant (P<0.05), Tm groups and MG group serum CD4+ cells/CD8+ cells was statistically significant (P<0.05); Tm and MG/AD group serum, C3 statistically significant (P<0.05); Tm and MG/AD group serum, CRP statistically significant (P<0.05); Tm groups and AD group serum IgE cells was statistically significant (P<0.05); (II) in thymoma tissus, the level of

  5. [Myasthenia in an epileptic patient].

    PubMed

    Sobolewski, P

    1996-01-01

    The author described a case of myasthenia and epilepsy in a female aged 36 years. The relationship between myasthenia and epilepsy was discussed. The additional factor which made the diagnosis difficult is bilateral deafness. PMID:9148180

  6. Sjögren syndrome and neuromyelitis optica spectrum disorder co-exist in a common autoimmune milieu.

    PubMed

    Carvalho, Diogo C; Tironi, Tauana S; Freitas, Denise S; Kleinpaul, Rodrigo; Talim, Natalia C; Lana-Peixoto, Marco A

    2014-08-01

    The relationship between Sjögren's syndrome (SS) and neuromyelitis optica spectrum disorder (NMOSD) is not completely understood. We report two patients with both conditions and review 47 other previously reported cases meeting currently accepted diagnostic criteria, from 17 articles extracted from PubMed. Out of 44 patients whose gender was informed, 42 were females. Mean age at onset of neurological manifestation was 36.2 years (10-74). Serum anti-AQP4-IgG was positive in 32 patients, borderline in 1, and negative in 4. Our Case 1 was seronegative for AQP4-IgG and had no non-organ-specific autoantibodies other than anti-SSB antibodies. Our Case 2 had serum anti-AQP4, anti-SSA/SSB, anti-thyreoglobulin and anti-acethylcholine-receptor antibodies, as well as clinical hypothyreoidism, but no evidence of myasthenia gravis. Our Cases and others, as previously reported in literature, with similar heterogeneous autoimmune response to aquaporin-4, suggest that SS and NMO co-exist in a common autoimmune milieu which is not dependent on aquaporin-4 autoimmunity. PMID:25098478

  7. Therapeutic plasma exchange in a patient with myasthenia gravis.

    PubMed

    Dyar, Kelly L

    2013-01-01

    Tom was an interesting combination of a patient requiring both renal placement therapy and TPE. Because there are available through the inpatient dialysis unit, it provided an opportunity to educate Tom on apheresis treatments as well as treatment options for chronic disease. Discussion with Tom during these treatments revealed that he wanted to retain as much autonomy and responsibility for his care as possible. Collaboration with the nephrologists and neurologist, as well as the outpatient infusion center, allowed Tom to schedule treatments before he experienced a myasthenic crisis but also hospitalization, which could increase his risk of infection. The time he spent receiving the TPE treatments was a unique and wonderful opportunity to answer all of Tom's questions about treatment modalities and allowed nursing staff to advocate fully for his wishes. At the time of this writing, Tom has remained free of myasthenic symptoms and has not required TPE treatments for over two years. PMID:24579400

  8. Infections and autoimmune diseases.

    PubMed

    Bach, Jean-François

    2005-01-01

    The high percentage of disease-discordant pairs of monozygotic twins demonstrates the central role of environmental factors in the etiology of autoimmune diseases. Efforts were first focussed on the search for triggering factors. The study of animal models has clearly shown that infections may trigger autoimmune diseases, as in the case of Coxsackie B4 virus in type I diabetes and the encephalomyocarditis virus in autoimmune myositis, two models in which viruses are thought to act by increasing immunogenicity of autoantigens secondary to local inflammation. The induction of a Guillain-Barré syndrome in rabbits after immunization with a peptide derived from Campylobacter jejuni is explained by mimicry between C. jejuni antigens and peripheral nerve axonal antigens. Other models involve chemical modification of autoantigens, as in the case of iodine-induced autoimmune thyroiditis. These mechanisms have so far only limited clinical counterparts (rheumatic fever, Guillain-Barré syndrome and drug-induced lupus or myasthenia gravis) but one may assume that unknown viruses may be at the origin of a number of chronic autoimmune diseases, such as type I diabetes and multiple sclerosis) as illustrated by the convergent data incriminating IFN-alpha in the pathophysiology of type I diabetes and systemic lupus erythematosus. Perhaps the difficulties met in identifying the etiologic viruses are due to the long lag time between the initial causal infection and onset of clinical disease. More surprisingly, infections may also protect from autoimmune diseases. Western countries are being confronted with a disturbing increase in the incidence of most immune disorders, including autoimmune and allergic diseases, inflammatory bowel diseases, and some lymphocyte malignancies. Converging epidemiological evidence indicates that this increase is linked to improvement of the socio-economic level of these countries, posing the question of the causal relationship and more precisely the

  9. Outcome of Extended Thymectomy in Myasthenia Crisis Patient.

    PubMed

    Aftabuddin, M; Bhandari, S

    2016-07-01

    Myasthenic crisis is a life-threatening condition. We studied the demographic, frequency, causes and clinical presentation of isolated Myasthenic crisis, steps of treatment and to review our experience of extended thymectomy on patients with at least one episode myasthenic crisis. A prospective and retrospective study was conducted on patients with at least one episode of myasthenic crisis, from March 2010 to September 2014, at the Department of Cardiac Surgery, BSMMU, Dhaka, Bangladesh who were referred for thymectomy. Eighteen patients (13.6% of the total 132 patients with myasthenia gravis were admitted with single to multiple episodes of myasthenic crisis, median crisis was 2.5 episodes. Mean age of the patient was 35.5 (18-72) years with male predominance. All eighteen patients had undergone extended thymectomy after completion of 5 cycle plasmapheresis, of which 2 had experienced postoperative respiratory crisis, required invasive ventilator support for median 14 days. One patient required invasive ventilator support after third post operative day. Six patients had thymoma and 12 had thymic hyperplasia. Three patients needed Intravenous immunoglobin. Nine patients needed post operative anti acetylcholinesterase inhibitor after median 2.5 post days. Post thymectomy remission and decreases the frequency of myasthenic crisis was seen in follow up and post operative medication requirement reduced significantly as compared to the preoperative requirement. This report highlights that the patients who had extended thymectomy after episodes of myasthenia crisis are benefitted even in the histhopathology report does not confirmed thymoma. After thymectomy, there was remission of myasthenic crisis. Patients with myasthenic crisis should have judicious drug adjustments under supervision and should be treated aggressively during impending myasthenic crisis. With modern management of myasthenia gravis, early surgery with myasthenic crisis is safe with good long

  10. Surgery Effective Against Immune Disorder That Weakens Muscles

    MedlinePlus

    ... html Surgery Effective Against Immune Disorder That Weakens Muscles Myasthenia gravis affects 60,000 Americans, but removal ... gravis, an autoimmune disorder that causes life-threatening muscle weakness, researchers report. Since the 1940s, doctors have ...

  11. A review of the current literature and a guide to the early diagnosis of autoimmune disorders associated with neuromyelitis optica.

    PubMed

    Iyer, Anand; Elsone, Liene; Appleton, Richard; Jacob, Anu

    2014-05-01

    Neuromyelitis optica (NMO) is an immune-mediated neurological disorder characterised by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis. A serum biomarker, aquaporin-4 IgG, the autoantibody against aquaporin-4 water channel, has been specifically associated with NMO and has assisted early recognition and prediction of relapses. Less commonly, a monophasic course, associated with antibodies to myelin oligodendrocyte glycoprotein has been reported. Specific diagnostic criteria have been defined; however, some cases that do not fulfil these criteria (but are nevertheless associated with aquaporin-4 IgG) are classified as NMO spectrum disorder and follow the same relapsing course. An ever-growing list of autoimmune disorders, both organ-specific and non-organ-specific, have been associated in up to 20-30% of patients with NMO. These disorders, which may become symptomatic before or after the development of NMO, are often diagnosed long after the diagnosis of NMO, as symptoms may be wrongly attributed to NMO, its residual effects or medication side effects. In addition, autoantibodies can be found in patients with NMO without coexisting disease (up to 40% in some series) and maybe suggestive of a heightened humoral immune response. We present a comprehensive review of the current literature on autoimmune disorders co-existing with NMO and identified 22 autoimmune conditions (myasthenia gravis, coeliac disease, ulcerative colitis, sclerosing cholangitis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid antibody syndrome, Sjogren's syndrome, autoimmune hypothyroidism, immune thrombocytopenic purpura, pernicious anaemia, narcolepsy, pemphigus foliaceus, alopecia areata, psoriasis, scleroderma, dermatitis herpetiformis, polymyositis, chronic inflammatory demyelinating polyneuropathy, paraneoplastic disorders, insulin dependent diabetes mellitus and autoimmune encephalitis). PMID:24512514

  12. Same-sex marriage, autoimmune thyroid gland dysfunction and other autoimmune diseases in Denmark 1989-2008.

    PubMed

    Frisch, Morten; Nielsen, Nete Munk; Pedersen, Bo Vestergaard

    2014-01-01

    Autoimmune diseases have been little studied in gay men and lesbians. We followed 4.4 million Danes, including 9,615 same-sex married (SSM) persons, for 47 autoimmune diseases in the National Patient Registry between 1989 and 2008. Poisson regression analyses provided first hospitalization rate ratios (RRs) comparing rates between SSM individuals and persons in other marital status categories. SSM individuals experienced no unusual overall risk of autoimmune diseases. However, the risk of autoimmune thyroid dysfunction was increased, notably Hashimoto's thyroiditis (women(SSM), RR = 2.92; 95% confidence interval (CI) 1.74-4.55) and Graves' disease (men(SSM), RR = 1.88; 95% CI 1.08-3.01). There was also an excess of primary biliary cirrhosis (women(SSM), RR = 4.09; 95% CI 1.01-10.7), and of psoriasis (men(SSM), RR = 2.48; 95% CI 1.77-3.36), rheumatic fever (men(SSM), RR = 7.55; 95% CI 1.87-19.8), myasthenia gravis (men(SSM), RR = 5.51; 95% CI 1.36-14.4), localized scleroderma (men(SSM), RR = 7.16; 95% CI 1.18-22.6) and pemphigoid (men(SSM), RR = 6.56; 95% CI 1.08-20.6), while Dupuytren's contracture was reduced (men(SSM), RR = 0.64; 95% CI 0.39-0.99). The excess of psoriasis was restricted to same-sex married men with HIV/AIDS (men(SSM), RR = 10.5; 95% CI 6.44-15.9), whereas Graves' disease occurred in excess only among same-sex married men without HIV/AIDS (men(SSM), RR = 1.99; 95% CI 1.12-3.22). Lesbians and immunologically competent gay men in same-sex marriage face no unusual overall risk of autoimmune diseases. However, the observed increased risk of thyroid dysfunction in these lesbians and gay men deserves further study. PMID:24306355

  13. 9 CFR 319.313 - Beef with gravy and gravy with beef.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Beef with gravy and gravy with beef... Dehydrated Meat Food Products § 319.313 Beef with gravy and gravy with beef. “Beef with Gravy” and “Gravy with Beef” shall not be made with beef which, in the aggregate for each lot contains more than...

  14. 9 CFR 319.313 - Beef with gravy and gravy with beef.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Beef with gravy and gravy with beef... Dehydrated Meat Food Products § 319.313 Beef with gravy and gravy with beef. “Beef with Gravy” and “Gravy with Beef” shall not be made with beef which, in the aggregate for each lot contains more than...

  15. Autoantibodies to glutathione S-transferase theta 1 in patients with primary sclerosing cholangitis and other autoimmune diseases.

    PubMed

    Ardesjö, Brita; Hansson, Caisa M; Bruder, Carl E G; Rorsman, Fredrik; Betterle, Corrado; Dumanski, Jan P; Kämpe, Olle; Ekwall, Olov

    2008-06-01

    Primary sclerosing cholangitis (PSC) is an enigmatic disorder with a suggested autoimmune basis. A variety of autoantigens have been suggested but no specific or highly directed epitope has been identified. To address this issue, we constructed a cDNA library from normal human choledochus and screened expressing clones with serum from a patient with PSC and inflammatory bowel disease (IBD). Based on this screening, glutathione S-transferase theta 1 (GSTT1) was identified as a potential autoantigenic target. To study the specificity of GSTT1, we determined immunoreactivity using a panel of 58 patients with PSC, with and without IBD, 57 patients with IBD, 31 patients with Hashimoto's thyroiditis, 30 patients with primary biliary cirrhosis (PBC), 20 patients with insulin dependent diabetes mellitus, 22 patients with autoimmune polyendocrine syndrome type I, 10 patients with systemic lupus erythematosus (SLE), 20 patients with Sjögren's syndrome, 12 patients with autoimmune pancreatitis, 28 patients with Addison's disease, 27 patients with Grave's disease, 17 with myasthenia gravis, and 118 healthy controls. Reactivity against GSTT1 was found with PSC and IBD as well as some patients with other autoimmune pathology, indicating that this population of antibodies is neither specific nor a sensitive serologic marker for PSC, but the frequency was clearly higher in autoimmune patients than controls. GSTT1-antibodies have been described in persons with GSTT1-null genotype and are suggested to develop as an alloimmune response to blood transfusions from GSTT1-positive donors or pregnancies with GSTT1-positive children. Therefore, two IBD patients with and 15 PSC patients without GSTT1-antibodies were genotyped for GSTT1 to investigate if the presence of GSTT1-antibodies was associated with the GSTT1-null genotype and possibly caused by an alloimmune response. Both IBD patients and three of the PSC patients were of the GSTT1-null genotype. We note that the frequency of GSTT1

  16. Myasthenia in pregnancy: best practice guidelines from a U.K. multispecialty working group.

    PubMed

    Norwood, Fiona; Dhanjal, Mandish; Hill, Marguerite; James, Natalie; Jungbluth, Heinz; Kyle, Pippa; O'Sullivan, Geraldine; Palace, Jacqueline; Robb, Stephanie; Williamson, Catherine; Hilton-Jones, David; Nelson-Piercy, Catherine

    2014-05-01

    A national U.K. workshop to discuss practical clinical management issues related to pregnancy in women with myasthenia gravis was held in May 2011. The purpose was to develop recommendations to guide general neurologists and obstetricians and facilitate best practice before, during and after pregnancy. The main conclusions were (1) planning should be instituted well in advance of any potential pregnancy to allow time for myasthenic status and drug optimisation; (2) multidisciplinary liaison through the involvement of relevant specialists should occur throughout pregnancy, during delivery and in the neonatal period; (3) provided that their myasthenia is under good control before pregnancy, the majority of women can be reassured that it will remain stable throughout pregnancy and the postpartum months; (4) spontaneous vaginal delivery should be the aim and actively encouraged; (5) those with severe myasthenic weakness need careful, multidisciplinary management with prompt access to specialist advice and facilities; (6) newborn babies born to myasthenic mothers are at risk of transient myasthenic weakness, even if the mother's myasthenia is well-controlled, and should have rapid access to neonatal high-dependency support. PMID:23757420

  17. Pyridostigmine but not 3,4-diaminopyridine exacerbates ACh receptor loss and myasthenia induced in mice by muscle-specific kinase autoantibody.

    PubMed

    Morsch, Marco; Reddel, Stephen W; Ghazanfari, Nazanin; Toyka, Klaus V; Phillips, William D

    2013-05-15

    In myasthenia gravis, the neuromuscular junction is impaired by the antibody-mediated loss of postsynaptic acetylcholine receptors (AChRs). Muscle weakness can be improved upon treatment with pyridostigmine, a cholinesterase inhibitor, or with 3,4-diaminopyridine, which increases the release of ACh quanta. The clinical efficacy of pyridostigmine is in doubt for certain forms of myasthenia. Here we formally examined the effects of these compounds in the antibody-induced mouse model of anti-muscle-specific kinase (MuSK) myasthenia gravis. Mice received 14 daily injections of IgG from patients with anti-MuSK myasthenia gravis. This caused reductions in postsynaptic AChR densities and in endplate potential amplitudes. Systemic delivery of pyridostigmine at therapeutically relevant levels from days 7 to 14 exacerbated the anti-MuSK-induced structural alterations and functional impairment at motor endplates in the diaphragm muscle. No such effect of pyridostigmine was found in mice receiving control human IgG. Mice receiving smaller amounts of MuSK autoantibodies did not display overt weakness, but 9 days of pyridostigmine treatment precipitated generalised muscle weakness. In contrast, one week of treatment with 3,4-diaminopyridine enhanced neuromuscular transmission in the diaphragm muscle. Both pyridostigmine and 3,4-diaminopyridine increase ACh in the synaptic cleft yet only pyridostigmine potentiated the anti-MuSK-induced decline in endplate ACh receptor density. These results thus suggest that ongoing pyridostigmine treatment potentiates anti-MuSK-induced AChR loss by prolonging the activity of ACh in the synaptic cleft. PMID:23440963

  18. Pyridostigmine but not 3,4-diaminopyridine exacerbates ACh receptor loss and myasthenia induced in mice by muscle-specific kinase autoantibody

    PubMed Central

    Morsch, Marco; Reddel, Stephen W; Ghazanfari, Nazanin; Toyka, Klaus V; Phillips, William D

    2013-01-01

    In myasthenia gravis, the neuromuscular junction is impaired by the antibody-mediated loss of postsynaptic acetylcholine receptors (AChRs). Muscle weakness can be improved upon treatment with pyridostigmine, a cholinesterase inhibitor, or with 3,4-diaminopyridine, which increases the release of ACh quanta. The clinical efficacy of pyridostigmine is in doubt for certain forms of myasthenia. Here we formally examined the effects of these compounds in the antibody-induced mouse model of anti-muscle-specific kinase (MuSK) myasthenia gravis. Mice received 14 daily injections of IgG from patients with anti-MuSK myasthenia gravis. This caused reductions in postsynaptic AChR densities and in endplate potential amplitudes. Systemic delivery of pyridostigmine at therapeutically relevant levels from days 7 to 14 exacerbated the anti-MuSK-induced structural alterations and functional impairment at motor endplates in the diaphragm muscle. No such effect of pyridostigmine was found in mice receiving control human IgG. Mice receiving smaller amounts of MuSK autoantibodies did not display overt weakness, but 9 days of pyridostigmine treatment precipitated generalised muscle weakness. In contrast, one week of treatment with 3,4-diaminopyridine enhanced neuromuscular transmission in the diaphragm muscle. Both pyridostigmine and 3,4-diaminopyridine increase ACh in the synaptic cleft yet only pyridostigmine potentiated the anti-MuSK-induced decline in endplate ACh receptor density. These results thus suggest that ongoing pyridostigmine treatment potentiates anti-MuSK-induced AChR loss by prolonging the activity of ACh in the synaptic cleft. PMID:23440963

  19. Current approach to seronegative myasthenia.

    PubMed

    Argov, Zohar

    2011-01-01

    The group of patients with weakness or fatigue who have electrophysiological evidence of neuromuscular transmission defects, but no antibodies against either acetyl choline receptor or muscle specific kinase, need special evaluation and therapeutic consideration. Such seronegative patients may have low affinity antibodies but may also be late onset of a congenital myasthenic syndrome. This review discuss the practical approach toward the condition of seronegative myasthenia. PMID:20852878

  20. [Autoimmune diseases with the presence of anti-ku antibodies - analysis of three cases].

    PubMed

    Wielosz, Ewa; Majdan, Maria; Jeleniewicz, Radosław; Mazurek, Marcin

    2016-01-01

    a-Ku are rare antibodies, which are reported in course of connective tissue diseases. Their prevalence ranges from 0 to 10% , 2%, on average. The main symptoms associated with the presence of a-Ku antibodies include: myositis, arthritis, Raynaud`s phenomenon and skin lesions. The above features are often defined as autoimmune clinical syndrome associated with a-Ku antibodies. In recent years, three cases with the presence of a-Ku antibodies were observed at the Department of Rheumatology and Connective Tissue Diseases. Case 1, a 77-year-old man, with the diagnosis of mixed connective tissue disease according to Raynaud`s phenomenon, myositis, arthritis and presence of a-ribonucleoprotein antibodies. Moreover, secondary Sjögren syndrome (SS) and myasthenia gravis were diagnosed. Case 2, a 56-year-old woman with longstanding history of Raynaud`s phenomenon, sclerodactyly, myositis and arthritis. Based on clinical manifestations and additional tests, systemic sclerosis and myositis were diagnosed. Case 3, a 46-year-old woman with SS diagnosis, long-standing history of Raynaud`s phenomenon, arthralgia and polyneuropathy. Moreover, HCV infection with the presence of cryoglobulin was confirmed. The presence of a-Ku antibodies in high titers was found in all cases. The clinical conditions improved after steroid and immunosuppressive therapy. In conclusion, clinical syndromes with the presence of a-Ku antibodies are associated with a wide range of non-specific symptoms, regarding muscle, joint and skin involvement, in particular. The conditions are more often diagnosed in the elderly; in the majority of cases, they are characterized by mild courses, good response to steroid therapy and good prognosis. PMID:27162291

  1. Autoimmune Hepatitis

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Autoimmune Hepatitis Page Content On this page: What is autoimmune ... Points to Remember Clinical Trials What is autoimmune hepatitis? Autoimmune hepatitis is a chronic—or long lasting— ...

  2. Computed tomography of the anterior mediastinum in myasthemia gravis: a radiologic-pathologic correlative study

    SciTech Connect

    Fon, G.T.; Bein, M.E.; Mancuso, A.A.; Keesey, J.C.; Lupetin, A.R.; Wong, W.S.

    1982-01-01

    Chest radiographs and computed tomographic (CT) scans of the mediastinum were correlated with pathologic findings of the thymus following thymectomy in 57 patients with myasthenia gravis. Based on the patient's age and the overall morphology of the anterior mediastinum, CT scans were assigned one of four grades in an attempt to predict thymus pathologic findings. Using this grading, 14 of 16 cases of thymoma were suspected or definitely diagnosed. One of the two cases not diagnosed on CT was a microscopic tumor. There were no false-positive diagnoses in 11 cases graded as definitely thymoma. We conclude that thymoma can be sensitively diagnosed in patients older than 40 years of age. However, thymoma cannot be predicted with a high level of confidence in patients younger than 40 because of the difficulty in differentiating normal thymus or hyperplasia from thymoma. Recommendations for the use of CT in the preoperative evaluation of myasthenic patients are presented.

  3. In vivo Therapy with Monoclonal Anti-I-A Antibody Suppresses Immune Responses to Acetylcholine Receptor

    NASA Astrophysics Data System (ADS)

    Waldor, Matthew K.; Sriram, Subramaniam; McDevitt, Hugh O.; Steinman, Lawrence

    1983-05-01

    A monoclonal antibody to I-A gene products of the immune response gene complex attenuates both humoral and cellular responses to acetylcholine receptor and appears to suppress clinical manifestations of experimental autoimmune myasthenia gravis. This demonstrates that use of antibodies against immune response gene products that are associated with susceptibility to disease may be feasible for therapy in autoimmune conditions such as myasthenia gravis.

  4. 9 CFR 319.313 - Beef with gravy and gravy with beef.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    .... 319.313 Section 319.313 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Canned, Frozen, or Dehydrated Meat Food Products § 319.313 Beef with gravy and gravy with beef. “Beef with Gravy” and...

  5. 9 CFR 319.313 - Beef with gravy and gravy with beef.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .... 319.313 Section 319.313 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Canned, Frozen, or Dehydrated Meat Food Products § 319.313 Beef with gravy and gravy with beef. “Beef with Gravy” and...

  6. 9 CFR 319.313 - Beef with gravy and gravy with beef.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    .... 319.313 Section 319.313 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Canned, Frozen, or Dehydrated Meat Food Products § 319.313 Beef with gravy and gravy with beef. “Beef with Gravy” and...

  7. Autoimmune hepatitis

    MedlinePlus

    ... diseases. These include: Graves disease Inflammatory bowel disease Rheumatoid arthritis Scleroderma Sjogren syndrome Systemic lupus erythematosus Thyroiditis Type 1 diabetes Ulcerative colitis Autoimmune hepatitis may occur in family ...

  8. Autoimmune myelopathies.

    PubMed

    Flanagan, Eoin P

    2016-01-01

    Autoimmune myelopathies are a heterogeneous group of immune-mediated spinal cord disorders with a broad differential diagnosis. They encompass myelopathies with an immune attack on the spinal cord (e.g., aquaporin-4-IgG (AQP4-IgG) seropositive neuromyelitis optica (NMO) and its spectrum disorders (NMOSD)), myelopathies occurring with systemic autoimmune disorders (which may also be due to coexisting NMO/NMOSD), paraneoplastic autoimmune myelopathies, postinfectious autoimmune myelopathies (e.g., acute disseminated encephalomyelitis), and myelopathies thought to be immune-related (e.g., multiple sclerosis and spinal cord sarcoidosis). Spine magnetic resonance imaging is extremely useful in the evaluation of autoimmune myelopathies as the location of signal change, length of the lesion, gadolinium enhancement pattern, and evolution over time narrow the differential diagnosis considerably. The recent discovery of multiple novel neural-specific autoantibodies accompanying autoimmune myelopathies has improved their classification. These autoantibodies may be pathogenic (e.g., AQP4-IgG) or nonpathogenic and more reflective of a cytotoxic T-cell-mediated autoimmune response (collapsin response mediator protein-5(CRMP5)-IgG). The presence of an autoantibody may help guide cancer search, assist treatment decisions, and predict outcome/relapse. With paraneoplastic myelopathies the initial goal is detection and treatment of the underlying cancer. The aim of immunotherapy in all autoimmune myelopathies is to maximize reversibility, maintain benefits (while preventing relapse), and minimize side effects. PMID:27112686

  9. Status of the thymectomy trial for nonthymomatous myasthenia gravis patients receiving prednisone.

    PubMed

    Newsom-Davis, John; Cutter, Gary; Wolfe, Gil I; Kaminski, Henry J; Jaretzki, Alfred; Minisman, Greg; Aban, Inmaculada; Conwit, Robin

    2008-01-01

    The primary study [MGTX] aims to answer three questions: does extended transsternal thymectomy combined with the prednisone protocol, when compared with the prednisone protocol alone: (1) result in a greater improvement in myasthenic weakness, (2) result in a lower total dose of prednisone, thus decreasing the likelihood of concurrent and long-term toxic effects, (3) enhance the quality of life by reducing adverse events and symptoms associated with the therapies? Inclusion criteria are MGFA Class 2, 3, or 4; acetylcholine receptor antibody positive; age at least 18.0 years and <60.0 years; MG history of <3 years. Patients can be prednisone naïve or not. The National Institute for Neurological Disorders and Stroke awarded funding for MGTX in September 2005, and NIH awarded funding for the ancillary Biomarkers study (BioMG) in February 2006. Diverse regulatory obstacles have been encountered in this international study, but we now have a total of over 70 centers in 22 countries (North America, South America, Europe, Australasia, South Africa) either actively recruiting or at various levels of readiness. PMID:18567886

  10. Identification and characterization of a new multigene family in the human MHC: A candidate autoimmune disease susceptibility element (3.8-1)

    SciTech Connect

    Harris, J.M.; Venditti, C.P.; Chorney, M.J.

    1994-09-01

    An association between idiopathic hemochromatosis (HFE) and the HLA-A3 locus has been previously well-established. In an attempt to identify potential HFE candidate genes, a genomic DNA fragment distal to the HLA-A9 breakpoint was used to screen a B cell cDNA library; a member (3.8-1) of a new multigene family, composed of five distinct genomic cross-reactive fragments, was identified. Clone 3.8-1 represents the 3{prime} end of 9.6 kb transcript which is expressed in multiple tissues including the spleen, thymus, lung and kidney. Sequencing and genome database analysis indicate that 3.8-1 is unique, with no homology to any known entries. The genomic residence of 3-8.1, defined by polymorphism analysis and physical mapping using YAC clones, appears to be absent from the genomes of higher primates, although four other cross-reactivities are maintained. The absence of this gene as well as other probes which map in the TNF to HLA-B interval, suggest that this portion of the human HMC, located between the Class I and Class III regions, arose in humans as the result of a post-speciation insertional event. The large size of the 3.8-1 gene and the possible categorization of 3.8-1 as a human-specific gene are significant given the genetic data that place an autoimmune susceptibility element for IDDM and myasthenia gravis in the precise region where this gene resides. In an attempt to isolate the 5{prime} end of this large transcript, we have constructed a cosmid contig which encompasses the genomic locus of this gene and are progressively isolating coding sequences by exon trapping.

  11. Autoimmune hepatitis

    MedlinePlus

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  12. Autoimmune disorders

    MedlinePlus

    ... exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or viruses) or drugs may trigger changes that confuse the immune system. This may happen ...

  13. [Autoimmune encephalitis].

    PubMed

    Davydovskaya, M V; Boyko, A N; Beliaeva, I A; Martynov, M Yu; Gusev, E I

    2015-01-01

    The authors consider the issues related to pathogenesis, clinical features, diagnosis and treatment of autoimmune encephalitis. It has been demonstrated that the development of autoimmune encephalitis can be associated with the oncologic process or be of idiopathic character. The pathogenesis of autoimmune encephalitis is caused by the production of antibodies that directly or indirectly (via T-cell mechanism) damage exo-and/or endocellular structures of the nerve cells. The presence of antobodies to endocellular structures of neurons in the cerebrospinal fluid of patients with autoimmune encephalitis in the vast majority of cases (> 95%) indicates the concomitant oncologic process, the presence of antibodies to membranes or neuronal synapses can be not associated with the oncologic process. Along with complex examination, including neuroimaging, EEG, cerebrospinal fluid and antibodies, the diagnostic algorithm in autoimmune encephalitis should include the search for the nidus of cancer. The treatment algorithm in autoimmune encephalitis included the combined immunosupressive therapy, plasmapheresis, immunoglobulines, cytostatics as well as treatment of the oncologic process. PMID:26322363

  14. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota.

    PubMed Central

    Bartley, G B

    1994-01-01

    accompanied GO in approximately 4% and 1% of patients, respectively. Myasthenia gravis occurred in less than 1% of patients. Superior limbic keratoconjunctivitis was documented in less than 4% of patients. The median age at the time of diagnosis of GO was 43 years (range, 8 to 88). Among patients with hyperthyroidism, 61% developed ophthalmopathy within 1 year of the onset of thyrotoxicosis. Symptoms and signs for which statistically significant changes occurred between the initial and final examinations included lacrimation, pain or ocular discomfort, photophobia, eyelid retraction, lid lag, eyelid fullness, conjunctival injection, chemosis, and exophthalmos.(ABSTRACT TRUNCATED AT 400 WORDS) Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:7886878

  15. Acute Severe Animal Model of Muscle-Specific Kinase Myasthenia: Combined Postsynaptic and Presynaptic Changes

    PubMed Central

    Richman, David P.; Nishi, Kayoko; Morell, Stuart W.; Chang, Jolene Mi; Ferns, Michael J.; Wollmann, Robert L.; Maselli, Ricardo A.; Schnier, Joachim; Agius, Mark A.

    2014-01-01

    Objective To determine the pathogenesis of anti-muscle-specific kinase (MuSK) myasthenia, a newly described severe form of myasthenia gravis associated with MuSK antibodies, characterized by focal muscle weakness and wasting, and absence of acetylcholine receptor antibodies; also to determine whether antibodies to MuSK, a crucial protein in the formation of the neuromuscular junction (NMJ) during development, can induce disease in the mature NMJ. Design/Methods Lewis rats were immunized with a single injection of a newly discovered splicing variant of MuSK, MuSK 60, which has been demonstrated to be expressed primarily in the mature NMJ. Animals were assessed clinically, serologically and by repetitive stimulation of median nerve. Muscle tissue was examined immunohistochemically and by electron microscopy. Results Animals immunized with 100ug of MuSK 60 develop severe progressive weakness, starting at day 16, with 100% mortality by day 27. The weakness is associated with high MuSK antibody titers, weight loss, axial muscle wasting and decrementing compound muscle action potentials. Light and electron microscopy demonstrate fragmented NMJs with varying degrees of postsynaptic muscle endplate destruction along with abnormal nerve terminals, lack of registration between endplates and nerve terminals, local axon sprouting and extrajunctional dispersion of cholinesterase activity. Conclusions These findings: 1) support the role of MuSK antibodies in the human disease; 2) demonstrate the role of MuSK, not only in the development of the NMJ, but also in the maintenance of the mature synapse; and 3) demonstrate involvement in this disease of both pre- and post-synaptic components of the NMJ. PMID:22158720

  16. Vegetables, Soups, Sauces, Gravies and Beverages.

    ERIC Educational Resources Information Center

    Marine Corps Inst., Washington, DC.

    Developed as part of the Marine Corps Institute (MCI) correspondence training program, this course on vegetables, soups, sauces, gravies, and beverages is designed to increase Marine Corps cooks' effectiveness as food handlers, using the proper techniques in the preparation of these items. Introductory materials include specific information for…

  17. Autoimmune encephalopathies

    PubMed Central

    Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep

    2014-01-01

    Over the last 10 years the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of twelve autoimmune encephatilic disorders, grouped by syndromes and approached from a clinical perspective. Anti-NMDAR encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases. PMID:25315420

  18. Management of disease-modifying treatments in neurological autoimmune diseases of the central nervous system

    PubMed Central

    Salmen, A; Gold, R; Chan, A

    2014-01-01

    sclerosis. Clinical and Experimental Immunology 2014, 175: 373–84. CLIPPERS: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. Review of an increasingly recognized entity within the spectrum of inflammatory central nervous system disorders. Clinical and Experimental Immunology 2014, 175: 385–96. Requirement for safety monitoring for approved multiple sclerosis therapies: an overview. Clinical and Experimental Immunology 2014, 175: 397–407. Myasthenia gravis: an update for the clinician. Clinical and Experimental Immunology 2014, 175: 408–18. Cerebral vasculitis in adults: what are the steps in order to establish the diagnosis? Red flags and pitfalls. Clinical and Experimental Immunology 2014, 175: 419–24. Multiple sclerosis treatment and infectious issues: update 2013. Clinical and Experimental Immunology 2014, 175: 425–38. Diagnosis, pathogenesis and treatment of myositis: recent advances 2014, 175: 349–58. Neuromyelitis optica: clinical features, immunopathogenesis and treatment 2014, 176: 149–64. PMID:24358961

  19. Tensilon test

    MedlinePlus

    Myasthenia gravis-tensilon ... Tensilon tests to help tell the difference between myasthenia gravis and other conditions. ... The test helps: Diagnose myasthenia gravis Tell the difference between ... conditions Monitor treatment with oral anticholinesterase ...

  20. The autoimmune diseases

    SciTech Connect

    Rose, N.R.; Mackay, I.R.

    1985-01-01

    This book contains 25 chapters. Some of the chapter titles are: Genetic Predisposition to Autoimmune Diseases; Systemic Lupus Erythematosus; Autoimmune Aspects of Rheumatoid Arthritis; Immunology of Insulin-Dependent Diabetes; and Adrenal Autoimmunity and Autoimmune Polyglandular Syndromes.

  1. Autoimmune synaptopathies.

    PubMed

    Crisp, Sarah J; Kullmann, Dimitri M; Vincent, Angela

    2016-02-01

    Autoantibodies targeting proteins at the neuromuscular junction are known to cause several distinct myasthenic syndromes. Recently, autoantibodies targeting neurotransmitter receptors and associated proteins have also emerged as a cause of severe, but potentially treatable, diseases of the CNS. Here, we review the clinical evidence as well as in vitro and in vivo experimental evidence that autoantibodies account for myasthenic syndromes and autoimmune disorders of the CNS by disrupting the functional or structural integrity of synapses. Studying neurological and psychiatric diseases of autoimmune origin may provide new insights into the cellular and circuit mechanisms underlying a broad range of CNS disorders. PMID:26806629

  2. [Autoimmune encephalitis].

    PubMed

    Günther, Albrecht; Schubert, Julia; Brämer, Dirk; Witte, Otto Wilhelm

    2016-08-01

    Autoimmune encephalitis, an inflammatory disease of the brain, is usually attributed to antibody-mediated damage and dysfunction of neuronal structures. A distinction is made between onconeuronal antibodies (directed against intracellular neuronal antigens with resulting paraneoplastic neurological syndromes) and antibodies directed against neuronal cell surface proteins (with resulting synaptic encephalopathies). Anti-NMDA-Receptor-Encephalitis, the most common form of autoimmune encephalopathy, is characterized by a phased course of disease. Early disease phase involves nonspecific prodromes (fatigue, fever, headache) which lead to family doctor or emergency department consultation. Subsequently, neuropsychiatric behavioural problems, seizures, disturbance of memory and finally coma, dysautonomia and respiratory insufficiency often result in major complications (e.g. status epilepticus) necessitating intensive care treatment. The diagnosis is secured by detection of auto-antibodies in serum or cerebrospinal fluid. An intensive search for tumors is also recommended. The treatment of autoimmune encephalitis comprises of immunomodulatory and immunosuppessive strategies. Tumor therapy is the most important treatment of autoimmune encephalitis by onconeuronal antibodies. PMID:27557073

  3. Autoimmune Hepatitis

    MedlinePlus

    ... provider will closely monitor and manage any side effects that may occur, as high doses of prednisone are often prescribed to treat autoimmune hepatitis. Immune system suppressors. Medications that suppress the immune system prevent the body from making autoantibodies and block the immune reaction ...

  4. Autoimmune liver disease panel

    MedlinePlus

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider diagnose ...

  5. Obstetric and anesthetic management of severe congenital myasthenia syndrome.

    PubMed

    Terblanche, Nico; Maxwell, Cynthia; Keunen, Johannes; Carvalho, Jose C A

    2008-10-01

    The congenital myasthenia syndromes form a heterogeneous group of genetic diseases characterized by defective neuromuscular transmission. Although they have muscle fatigability in common with the acquired immune myasthenia syndrome, there are important pathophysiological, diagnostic, management and progression pattern differences between them. We report the management of a 28-yr-old patient with longstanding congenital myasthenia syndromes, who underwent an elective cesarean delivery under spinal anesthesia. Muscle imbalance plus weakness-related scoliosis and chronic respiratory failure complicated her management. Ultrasonography was used to facilitate the spinal anesthetic. Intraoperative noninvasive positive pressure ventilation maintained lung volumes effectively and prevented deterioration in respiratory function. PMID:18806046

  6. Autoimmune pancreatitis.

    PubMed

    Omiyale, Ayodeji Oluwarotimi

    2016-06-01

    Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids. PMID:27294040

  7. Autoimmune pancreatitis

    PubMed Central

    2016-01-01

    Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids. PMID:27294040

  8. Autoimmune Encephalitis

    PubMed Central

    Leypoldt, Frank; Wandinger, Klaus-Peter; Bien, Christian G; Dalmau, Josep

    2016-01-01

    The term autoimmune encephalitis is used to describe a group of disorders characterised by symptoms of limbic and extra-limbic dysfunction occurring in association with antibodies against synaptic antigens and proteins localised on the neuronal cell surface. In recent years there has been a rapidly expanding knowledge of these syndromes resulting in a shift in clinical paradigms and new insights into pathogenic mechanisms. Since many patients respond well to immunosuppressive treatment, the recognition of these disorders is of utmost importance. In general, there are no brain-imaging modalities or biomarkers specific of these disorders other than the demonstration of the neuronal antibodies. A disease classification based on these antibodies provides information on prognosis and paraneoplastic aetiology. This article focuses on recent clinical advances, newly characterised antibodies and treatment approaches to these disorders. PMID:27330568

  9. Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

    PubMed Central

    Faria, Ana M. C.; Weiner, Howard L.

    2006-01-01

    Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10) and Th3 (TGF-β) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB), Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE), uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy and early therapy. PMID:17162357

  10. Autoimmune Inner Ear Disease

    MedlinePlus

    ... Find an ENT Doctor Near You Autoimmune Inner Ear Disease Autoimmune Inner Ear Disease Patient Health Information ... with a hearing loss. How Does the Healthy Ear Work? The ear has three main parts: the ...

  11. Perspectives on autoimmunity

    SciTech Connect

    Cohen, I.R.

    1987-01-01

    The contents of this book are: HLA and Autoimmunity; Self-Recognition and Symmetry in the Immune System; Immunology of Insulin Dependent Diabetes Mellitus; Multiple Sclerosis; Autoimmunity and Immune Pathological Aspects of Virus Disease; Analyses of the Idiotypes and Ligand Binding Characteristics of Human Monoclonal Autoantibodies to DNA: Do We Understand Better Systemic Lupus Erythematosus. Autoimmunity and Rheumatic Fever; Autoimmune Arthritis Induced by Immunization to Mycobacterial Antigens; and The Interaction Between Genetic Factors and Micro-Organisms in Ankylosing Spondylitis: Facts and Fiction.

  12. [Atopy and autoimmunity -- a case report].

    PubMed

    Alfaro, M; Tapadinhas, F; Neves, Am; Costa Trindade, J

    2007-01-01

    Atopy, immunodeficiency and autoimmunity are manifestations of immune system dysfunction. Classically atopy and autoimmunity are referred as distinct immunological reactions. Recent studies suggest the existence of common pathogenic mechanisms. We report the case of a teenager with familial history of asthma and miasthenia gravis in her mother (HLA- B8+) and personal history of recurrent upper respiratory infections from two to four years old, and pneumonia since five years old (3 or 4 episodes/ year, in three consecutive years), with associated dyspnoea and hypoxemia, requiring frequently hospital admission. Investigation was initially negative for atopy markers, and excluded other hypothesis as tuberculosis, cystic fibrosis, -1 antitrypsin deficiency, congenital heart disease, bronchopulmonary malformations or foreign body aspiration. Latter, further exams finally confirmed atopy with a raised IgE, positive RAST and cutaneous sensitivity tests (for house dust mites and pollen) and revealed circulating immune complexes and IgG 2, 3 e 4 deficit. Most frequent autoantibodies and precipitins study were negative, and histocompatibility antigens study revealed HLA- B8 (as her mother). Ventilation-perfusion scintigraphy and respiratory function tests were normal. Antihistamines, topical corticoids and bronchodilators were done with an excellent clinical response. At 16 years- old she is admitted again with the diagnosis of erythema nodosum and the clinical suspicion of Sweet's syndrome, having a good evolution. The relation between atopy and autoimmunity is enfatized by the authors. This simultaneous occurrence does not correspond merely to a statistical association, but may represent a global immune system impairment, with the involvement of different types of hypersensibility. PMID:17962891

  13. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2016-04-22

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  14. Environmental Basis of Autoimmunity.

    PubMed

    Floreani, Annarosa; Leung, Patrick S C; Gershwin, M Eric

    2016-06-01

    The three common themes that underlie the induction and perpetuation of autoimmunity are genetic predisposition, environmental factors, and immune regulation. Environmental factors have gained much attention for their role in triggering autoimmunity, with increasing evidence of their influence as demonstrated by epidemiological studies, laboratory research, and animal studies. Environmental factors known to trigger and perpetuate autoimmunity include infections, gut microbiota, as well as physical and environmental agents. To address these issues, we will review major potential mechanisms that underlie autoimmunity including molecular mimicry, epitope spreading, bystander activation, polyclonal activation of B and T cells, infections, and autoinflammatory activation of innate immunity. The association of the gut microbiota on autoimmunity will be particularly highlighted by their interaction with pharmaceutical agents that may lead to organ-specific autoimmunity. Nonetheless, and we will emphasize this point, the precise mechanism of environmental influence on disease pathogenesis remains elusive. PMID:25998909

  15. Neurophysiological Strategies for the Diagnosis of Disorders of the Neuromuscular Junction in Children

    ERIC Educational Resources Information Center

    Pitt, Matthew

    2008-01-01

    The disorders of the neuromuscular junction seen in children, the congenital myasthenic syndromes and autoimmune myasthenia gravis, are very rare. Their clinical symptoms and signs may be variable, most notably in the neonate and infant. They should enter the differential diagnosis of many different clinical presentations, such as "floppy infant"…

  16. Autoimmune liver disease, autoimmunity and liver transplantation.

    PubMed

    Carbone, Marco; Neuberger, James M

    2014-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune

  17. Metals and kidney autoimmunity.

    PubMed Central

    Bigazzi, P E

    1999-01-01

    The causes of autoimmune responses leading to human kidney pathology remain unknown. However, environmental agents such as microorganisms and/or xenobiotics are good candidates for that role. Metals, either present in the environment or administered for therapeutic reasons, are prototypical xenobiotics that cause decreases or enhancements of immune responses. In particular, exposure to gold and mercury may result in autoimmune responses to various self-antigens as well as autoimmune disease of the kidney and other tissues. Gold compounds, currently used in the treatment of patients with progressive polyarticular rheumatoid arthritis, can cause a nephrotic syndrome. Similarly, an immune-mediated membranous nephropathy frequently occurred when drugs containing mercury were commonly used. Recent epidemiologic studies have shown that occupational exposure to mercury does not usually result in autoimmunity. However, mercury induces antinuclear antibodies, sclerodermalike disease, lichen planus, or membranous nephropathy in some individuals. Laboratory investigations have confirmed that the administration of gold or mercury to experimental animals leads to autoimmune disease quite similar to that observed in human subjects exposed to these metals. In addition, studies of inbred mice and rats have revealed that a few strains are susceptible to the autoimmune effects of gold and mercury, whereas the majority of inbred strains are resistant. These findings have emphasized the importance of genetic (immunogenetic and pharmacogenetic) factors in the induction of metal-associated autoimmunity. (italic)In vitro(/italic) and (italic)in vivo(/italic) research of autoimmune disease caused by mercury and gold has already yielded valuable information and answered a number of important questions. At the same time it has raised new issues about possible immunostimulatory or immunosuppressive mechanisms of xenobiotic activity. Thus it is evident that investigations of metal

  18. American Autoimmune Related Diseases Association

    MedlinePlus

    ... With #25FOR25 Campaign During National Autoimmune Disease Awareness Month AARDA officially kicks of National Autoimmune DIsease Awareness ... Click here to read more. Autoimmune Disease Awareness Month AARDA and the NCAPG held two important events ...

  19. The Autoimmune Ecology

    PubMed Central

    Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A.; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana

    2016-01-01

    Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures – internal and external – across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied. PMID:27199979

  20. The Autoimmune Ecology.

    PubMed

    Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana

    2016-01-01

    Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied. PMID:27199979

  1. Genetic basis of autoimmunity

    PubMed Central

    Marson, Alexander; Housley, William J.; Hafler, David A.

    2015-01-01

    Autoimmune diseases affect up to approximately 10% of the population. While rare Mendelian autoimmunity syndromes can result from monogenic mutations disrupting essential mechanisms of central and peripheral tolerance, more common human autoimmune diseases are complex disorders that arise from the interaction between polygenic risk factors and environmental factors. Although the risk attributable to most individual nucleotide variants is modest, genome-wide association studies (GWAS) have the potential to provide an unbiased view of biological pathways that drive human autoimmune diseases. Interpretation of GWAS requires integration of multiple genomic datasets including dense genotyping, cis-regulatory maps of primary immune cells, and genotyped studies of gene expression in relevant cell types and cellular conditions. Improved understanding of the genetic basis of autoimmunity may lead to a more sophisticated understanding of underlying cellular phenotypes and, eventually, novel diagnostics and targeted therapies. PMID:26030227

  2. Autoimmune autonomic disorders.

    PubMed

    Mckeon, Andrew; Benarroch, Eduardo E

    2016-01-01

    Autoimmune autonomic disorders occur because of an immune response directed against sympathetic, parasympathetic, and enteric ganglia, autonomic nerves, or central autonomic pathways. In general, peripheral autoimmune disorders manifest with either generalized or restricted autonomic failure, whereas central autoimmune disorders manifest primarily with autonomic hyperactivity. Some autonomic disorders are generalized, and others are limited in their anatomic extent, e.g., isolated gastrointestinal dysmotility. Historically, these disorders were poorly recognized, and thought to be neurodegenerative. Over the last 20 years a number of autoantibody biomarkers have been discovered that have enabled the identification of certain patients as having an autoimmune basis for either autonomic failure or hyperactivity. Peripheral autoimmune autonomic disorders include autoimmune autonomic ganglionopathy (AAG), paraneoplastic autonomic neuropathy, and acute autonomic and sensory neuropathy. AAG manifests with acute or subacute onset of generalized or selective autonomic failure. Antibody targeting the α3 subunit of the ganglionic-type nicotinic acetylcholine receptor (α3gAChR) is detected in approximately 50% of cases of AAG. Some other disorders are characterized immunologically by paraneoplastic antibodies with a high positive predictive value for cancer, such as antineuronal nuclear antibody, type 1 (ANNA-1: anti-Hu); others still are seronegative. Recognition of an autoimmune basis for autonomic disorders is important, as their manifestations are disabling, may reflect an underlying neoplasm, and have the potential to improve with a combination of symptomatic and immune therapies. PMID:27112689

  3. Autoimmunity in visual loss.

    PubMed

    Petzold, Axel; Wong, Sui; Plant, Gordon T

    2016-01-01

    There are a number of autoimmune disorders which can affect visual function. There are a very large number of mechanisms in the visual pathway which could potentially be the targets of autoimmune attack. In practice it is the retina and the anterior visual pathway (optic nerve and chiasm) that are recognised as being affected in autoimmune disorders. Multiple Sclerosis is one of the commonest causes of visual loss in young adults because of the frequency of attacks of optic neuritis in that condition, however the basis of the inflammation in Multiple Sclerosis and the confirmation of autoimmunity is lacking. The immune process is known to be highly unusual in that it is not systemic and confined to the CNS compartment. Previously an enigmatic partner to Multiple Sclerosis, Neuromyelitis Optica is now established to be autoimmune and two antibodies - to Aquaporin4 and to Myelin Oligodendrocyte Glycoprotein - have been implicated in the pathogenesis. The term Chronic Relapsing Inflammatory Optic Neuropathy is applied to those cases of optic neuritis which require long term immunosuppression and hence are presumed to be autoimmune but where no autoimmune pathogenesis has been confirmed. Optic neuritis occurring post-infection and post vaccination and conditions such as Systemic Lupus Erythematosus and various vasculitides may cause direct autoimmune attack to visual structures or indirect damage through occlusive vasculopathy. Chronic granulomatous disorders such as Sarcoidosis affect vision commonly by a variety of mechanisms, whether and how these are placed in the autoimmune panoply is unknown. As far as the retina is concerned Cancer Associated Retinopathy and Melanoma Associated Retinopathy are well characterised clinically but a candidate autoantibody (recoverin) is only described in the former disorder. Other, usually monophasic, focal retinal inflammatory disorders (Idiopathic Big Blind Spot Syndrome, Acute Zonal Occult Outer Retinopathy and Acute Macular

  4. Autoimmunity in picornavirus infections.

    PubMed

    Massilamany, Chandirasegaran; Koenig, Andreas; Reddy, Jay; Huber, Sally; Buskiewicz, Iwona

    2016-02-01

    Enteroviruses are small, non-enveloped, positive-sense single-strand RNA viruses, and are ubiquitously found throughout the world. These viruses usually cause asymptomatic or mild febrile illnesses, but have a propensity to induce severe diseases including type 1 diabetes and pancreatitis, paralysis and neuroinflammatory disease, myocarditis, or hepatitis. This pathogenicity may result from induction of autoimmunity to organ-specific antigens. While enterovirus-triggered autoimmunity can arise from multiple mechanisms including antigenic mimicry and release of sequestered antigens, the recent demonstration of T cells expressing dual T cell receptors arising as a natural consequence of Theiler's virus infection is the first demonstration of this autoimmune mechanism. PMID:26554915

  5. Autoimmune liver disease panel

    MedlinePlus

    ... common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care ... anti-mitochondrial antibodies, you are likely to have primary biliary cirrhosis. If the immune proteins are high and albumin ...

  6. Understanding Autoimmune Diseases

    MedlinePlus

    ... Autoimmune Diseases Progress and Promise Key Words The Immune System Your immune system is the network of cells and tissues throughout ... having two parts: the acquired and the innate immune systems. The acquired (or adaptive) immune system develops as ...

  7. Autoimmune Autonomic Ganglionopathy

    MedlinePlus

    ... usf.edu/ARDCRC/professional/register/index.htm Organizations Organizations Listen Nonprofit support and advocacy groups bring together ... endorsement by GARD. Suggest an organization to add. Organizations Supporting this Disease American Autoimmune Related Diseases Association ( ...

  8. Autoimmunity in 2014.

    PubMed

    Selmi, Carlo

    2015-10-01

    Our PubMed search for peer-reviewed articles published in the 2014 solar year retrieved a significantly higher number of hits compared to 2013 with a net 28 % increase. Importantly, full articles related to autoimmunity constitute approximately 5 % of immunology articles. We confirm that our understanding of autoimmunity is becoming a translational paradigm with pathogenetic elements rapidly followed by new treatment options. Furthermore, numerous clinical and pathogenetic elements and features are shared among autoimmune diseases, and this is well illustrated in the recent literature. More specifically, the past year witnessed critical revisions of our understanding and management of antiphospholipid syndrome with new exciting data on the pathogenicity of the serum anti-beta2 glycoprotein autoantibody, a better understanding of the current and new treatments for rheumatoid arthritis, and new position papers on important clinical questions such as vaccinations in patients with autoimmune disease, comorbidities, or new classification criteria. Furthermore, data confirming the important connections between innate immunity and autoimmunity via toll-like receptors or the critical role of T regulatory cells in tolerance breakdown and autoimmunity perpetuation were also reported. Lastly, genetic and epigenetic data were provided to confirm that the mosaic of autoimmunity warrants a susceptible individual background which may be geographically determined and contribute to the geoepidemiology of diseases. The 2014 literature in the autoimmunity world should be cumulatively regarded as part of an annus mirabilis in which, on a different level, the 2014 Annual Meeting of the American College of Rheumatology in Boston was attended by over 16,000 participants with over selected 3000 abstracts. PMID:26335699

  9. Silica, Silicosis, and Autoimmunity

    PubMed Central

    Pollard, Kenneth Michael

    2016-01-01

    Inhalation of dust containing crystalline silica is associated with a number of acute and chronic diseases including systemic autoimmune diseases. Evidence for the link with autoimmune disease comes from epidemiological studies linking occupational exposure to crystalline silica dust with the systemic autoimmune diseases systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Although little is known regarding the mechanism by which silica exposure leads to systemic autoimmune disease, there is a voluminous literature on silica exposure and silicosis that may help identify immune processes that precede development of autoimmunity. The pathophysiology of silicosis consists of deposition of silica particles in the alveoli of the lung. Ingestion of these particles by macrophages initiates an inflammatory response, which stimulates fibroblasts to proliferate and produce collagen. Silica particles are encased by collagen leading to fibrosis and the nodular lesions characteristic of the disease. The steps in the development of silicosis, including acute and chronic inflammation and fibrosis, have different molecular and cellular requirements, suggesting that silica-induced inflammation and fibrosis may be mechanistically separate. Significantly, it is unclear whether silica-induced inflammation and fibrosis contribute similarly to the development of autoimmunity. Nonetheless, the findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production, pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, and autoantibodies and tissue damage. The variable frequency of these immunological features following silica exposure suggests substantial genetic involvement and gene/environment interaction in silica-induced autoimmunity. However, numerous questions remain unanswered. PMID:27014276

  10. Silica, Silicosis, and Autoimmunity.

    PubMed

    Pollard, Kenneth Michael

    2016-01-01

    Inhalation of dust containing crystalline silica is associated with a number of acute and chronic diseases including systemic autoimmune diseases. Evidence for the link with autoimmune disease comes from epidemiological studies linking occupational exposure to crystalline silica dust with the systemic autoimmune diseases systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Although little is known regarding the mechanism by which silica exposure leads to systemic autoimmune disease, there is a voluminous literature on silica exposure and silicosis that may help identify immune processes that precede development of autoimmunity. The pathophysiology of silicosis consists of deposition of silica particles in the alveoli of the lung. Ingestion of these particles by macrophages initiates an inflammatory response, which stimulates fibroblasts to proliferate and produce collagen. Silica particles are encased by collagen leading to fibrosis and the nodular lesions characteristic of the disease. The steps in the development of silicosis, including acute and chronic inflammation and fibrosis, have different molecular and cellular requirements, suggesting that silica-induced inflammation and fibrosis may be mechanistically separate. Significantly, it is unclear whether silica-induced inflammation and fibrosis contribute similarly to the development of autoimmunity. Nonetheless, the findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production, pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, and autoantibodies and tissue damage. The variable frequency of these immunological features following silica exposure suggests substantial genetic involvement and gene/environment interaction in silica-induced autoimmunity. However, numerous questions remain unanswered. PMID:27014276

  11. Opportunistic autoimmune disorders

    PubMed Central

    Kong, Yi-chi M.; Wei, Wei-Zen; Tomer, Yaron

    2013-01-01

    Rapid advances in our understanding of the immune network have led to treatment modalities for malignancies and autoimmune diseases based on modulation of the immune response. Yet therapeutic modulation has resulted in immune dysregulation and opportunistic autoimmune sequelae, despite prescreening efforts in clinical trials. This review focuses on recent clinical data on opportunistic autoimmune disorders arising from three immunotherapeutic modalities: (1) systemic immunomodulators, including interferon-α (also used to treat hepatitis C patients) and interferon-β; (2) monoclonal antibodies to CTLA-4 and CD52, and (3) hematopoietic stem cell transplantation. Uncategorized predisposing factors in these patients include major histocompatibility complex and gender genetics, prevalence of different autoimmune diseases, prior chemotherapy, underlying disorder (e.g., hepatitis C), and preconditioning regimens as part of organ and stem cell transplants. Not unexpectedly, the prevalent autoimmune thyroid disease surfaced frequently. Our combination models to study the balance between thyroid autoimmunity and tumor immunity upon regulatory T-cell perturbation are briefly described. PMID:20146718

  12. Autoimmunity in 2013.

    PubMed

    Selmi, Carlo

    2014-08-01

    The peer-reviewed publications in the field of autoimmunity published in 2013 represented a significant proportion of immunology articles and grew since the previous year to indicate that more immune-mediated phenomena may recognize an autoimmune mechanism and illustrated by osteoarthritis and atherosclerosis. As a result, our understanding of the mechanisms of autoimmunity is becoming the paradigm for translational research in which the progress in disease pathogenesis for both tolerance breakdown and inflammation perpetuation is rapidly followed by new treatment approaches and clinical management changes. The similarities across the autoimmune disease spectrum outnumber differences, particularly when treatments are compared. Indeed, the therapeutics of autoimmune diseases are based on a growing armamentarium that currently includes monoclonal antibodies and small molecules which act by targeting molecular markers or intracellular mediators with high specificity. Among the over 100 conditions considered as autoimmune, the common grounds are well illustrated by the data reported for systemic lupus erythematosus and rheumatoid arthritis or by the plethora of studies on Th17 cells and biomarkers, particularly serum autoantibodies. Further, we are particularly intrigued by studies on the genomics, epigenetics, and microRNA at different stages of disease development or on the safe and effective use of abatacept acting on the costimulation of T and B cells in rheumatoid arthritis. We are convinced that the data published in 2013 represent a promising background for future developments that will exponentially impact the work of laboratory and clinical scientists over the next years. PMID:24819586

  13. Autoimmune movement disorders.

    PubMed

    Mckeon, Andrew; Vincent, Angela

    2016-01-01

    Autoimmune movement disorders encapsulate a large and diverse group of neurologic disorders occurring either in isolation or accompanying more diffuse autoimmune encephalitic illnesses. The full range of movement phenomena has been described and, as they often occur in adults, many of the presentations can mimic neurodegenerative disorders, such as Huntington disease. Disorders may be ataxic, hypokinetic (parkinsonism), or hyperkinetic (myoclonus, chorea, tics, and other dyskinetic disorders). The autoantibody targets are diverse and include neuronal surface proteins such as leucine-rich, glioma-inactivated 1 (LGI1) and glycine receptors, as well as antibodies (such as intracellular antigens) that are markers of a central nervous system process mediated by CD8+ cytotoxic T cells. However, there are two conditions, stiff-person syndrome (also known as stiff-man syndrome) and progressive encephalomyelitis with rigidity and myoclonus (PERM), that are always autoimmune movement disorders. In some instances (such as Purkinje cell cytoplasmic antibody-1 (PCA-1) autoimmunity), antibodies detected in serum and cerebrospinal fluid can be indicative of a paraneoplastic cause, and may direct the cancer search. In other instances (such as 65kDa isoform of glutamic acid decarboxylase (GAD65) autoimmunity), a paraneoplastic cause is very unlikely, and early treatment with immunotherapy may promote improvement or recovery. Here we describe the different types of movement disorder and the clinical features and antibodies associated with them, and discuss treatment. PMID:27112684

  14. Autoimmunity and Asbestos Exposure

    PubMed Central

    Pfau, Jean C.; Serve, Kinta M.; Noonan, Curtis W.

    2014-01-01

    Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA), a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a) a lack of statistical power due to relatively small or diffuse exposure cohorts, (b) exposure misclassification, (c) latency of clinical disease, (d) mild or subclinical entities that remain undetected or masked by other pathologies, or (e) effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease. PMID:24876951

  15. Autoimmune basal ganglia disorders.

    PubMed

    Dale, Russell C; Brilot, Fabienne

    2012-11-01

    The basal ganglia are deep nuclei in the brain that include the caudate, putamen, globus pallidus, and substantia nigra. Pathological processes involving the basal ganglia often result in disorders of movement and behavior. A number of different autoimmune disorders predominantly involve the basal ganglia and can result in movement and psychiatric disorders. The classic basal ganglia autoimmune disorder is Sydenham chorea, a poststreptococcal neuropsychiatric disorder. Resurgence in the interest in Sydenham chorea is the result of the descriptions of other poststreptococcal neuropsychiatric disorders including tics and obsessive-compulsive disorder, broadly termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Encephalitic processes affecting the basal ganglia are also described including the syndromes basal ganglia encephalitis, encephalitis lethargica, and bilateral striatal necrosis. Last, systemic autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome can result in chorea or parkinsonism. Using paradigms learned from other autoantibody associated disorders, the authors discuss the autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders. Identification of these entities is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system. PMID:22832771

  16. Experimental Autoimmune Breast Failure

    PubMed Central

    Kesaraju, Pavani; Jaini, Ritika; Johnson, Justin M.; Altuntas, Cengiz Z.; Gruden, Jessica J.; Sakalar, Cagri; Tuohy, Vincent K.

    2013-01-01

    Mastitis is a substantial clinical problem in lactating women that may result in severe pain and abrupt termination of breastfeeding, thereby predisposing infants to long-term health risks. Many cases of mastitis involve no known infectious agent and may fundamentally be due to autoimmune-mediated inflammation of the breast. Herein, we develop a murine model of autoimmune mastitis and provide a detailed characterization of its resulting phenotype of breast failure and lactation insufficiency. To generate breast-specific autoimmunity, we immunized SWXJ mice with recombinant mouse α-lactalbumin, a lactation-dependent, breast-specific differentiation protein critical for production of lactose. Mice immunized with α-lactalbumin showed extensive T-cell–mediated inflammation in lactating normal breast parenchyma but none in nonlactating normal breast parenchyma. This targeted autoimmune attack resulted in breast failure characterized by lactation insufficiency and decreased ability to nurture offspring. Although immunization with α-lactalbumin had no effect on fertility and birth numbers, pups nursed by α-lactalbumin–immunized mice showed significantly disrupted growth often accompanied by kwashiorkor-like nutritional abnormalities, including alopecia, liver toxicity, and runting. This experimental model of autoimmune breast failure has useful applications for prophylactic breast cancer vaccination and for addressing inflammatory complications during breastfeeding. In addition, this model is suited for investigating nutritionally based “failure-to-thrive” issues, particularly regarding the long-term implications of postnatal nutritional deprivation. PMID:22901749

  17. Reconceiving autoimmunity: An overview.

    PubMed

    Tauber, Alfred I

    2015-06-21

    Three interconnected positions are advocated: (1) although serving as a useful model, the immune self does not exist as such; (2) instead of a self/nonself demarcation, the immune system 'sees' itself, i.e., it does not ignore the 'self' or attack the 'other;' but exhibits a spectrum of responses, which when viewed from outside the system appear as discrimination of 'self' and 'nonself' based on certain criteria of reactivity. When immune reactions are conceived in terms of normal physiology and open exchange with the environment, where borders dividing host and foreign are elusive and changing, host defense is only part of the immune system's functions, which actually comprise two basic tasks: protection, i.e., to preserve host integrity, and maintenance of organismic identity. And thus (3) if the spectrum of immunity is enlarged, differentiating low reactive 'autoimmune' reactions from activated immune responses against the 'other' is only a matter of degree. Simply, all immunity is 'autoimmunity,' and the pathologic state of immunity directed at normal constituents of the organism is a particular case of dis-regulation, which appropriately is designated, autoimmune. Other uses of 'autoimmunity' and its congeners function as the semantic remnants of Burnet's original self/nonself theory and should be replaced. A new nomenclature is proposed, concinnity, which more accurately designates the physiology of the animal's ordinary housekeeping economy mediated by the immune system than 'autoimmunity' when used to describe such normal functions. PMID:24880023

  18. Pregnancy with autoimmune hepatitis

    PubMed Central

    Braga, António Costa; Vasconcelos, Carlos; Braga, Jorge

    2016-01-01

    Aim: The aim of this study was to review our experience with gestations in autoimmune hepatitis patients. Background: There are only limited data describing pregnancy in patients with autoimmune hepatitis. Patients and methods: Retrospective analysis of pregnancies with autoimmune hepatitis followed in Centro Hospitalar do Porto, Portugal in the last ten years. Results: We reported nine pregnancies in seven patients with autoimmune hepatitis. Two patients had documented liver cirrhosis prior to the pregnancy. In this study, 66.7% of patients were treated with azathioprine and 88.9% with prednisolone. Clinical improvements were observed in 11.1% of pregnancies and 22.2% exacerbations were diagnosed. There were six live births and two preterm deliveries (preterm delivery rate of 33%). We also report three first trimester miscarriages (early gestation miscarriage rate of 33%). There were no neonatal or maternal deaths. Conclusion: The favorable obstetric outcome is a realistic expectation in patients with autoimmune hepatitis. Tight monitoring and control of asymptomatic and unpredictable exacerbations, which are unrelated to the severity of the underlying disease, are essential to the prognosis of the current pregnancy. PMID:27458515

  19. Epigenetics and Autoimmune Diseases

    PubMed Central

    Quintero-Ronderos, Paula; Montoya-Ortiz, Gladis

    2012-01-01

    Epigenetics is defined as the study of all inheritable and potentially reversible changes in genome function that do not alter the nucleotide sequence within the DNA. Epigenetic mechanisms such as DNA methylation, histone modification, nucleosome positioning, and microRNAs (miRNAs) are essential to carry out key functions in the regulation of gene expression. Therefore, the epigenetic mechanisms are a window to understanding the possible mechanisms involved in the pathogenesis of complex diseases such as autoimmune diseases. It is noteworthy that autoimmune diseases do not have the same epidemiology, pathology, or symptoms but do have a common origin that can be explained by the sharing of immunogenetic mechanisms. Currently, epigenetic research is looking for disruption in one or more epigenetic mechanisms to provide new insights into autoimmune diseases. The identification of cell-specific targets of epigenetic deregulation will serve us as clinical markers for diagnosis, disease progression, and therapy approaches. PMID:22536485

  20. EBV and Autoimmunity.

    PubMed

    Ascherio, Alberto; Munger, Kassandra L

    2015-01-01

    Although a role of EBV in autoimmunity is biologically plausible and evidence of altered immune responses to EBV is abundant in several autoimmune diseases, inference on causality requires the determination that disease risk is higher in individuals infected with EBV than in those uninfected and that in the latter it increases following EBV infection. This determination has so far been possible only for multiple sclerosis (MS) and, to some extent, for systemic lupus erythematosus (SLE), whereas evidence is either lacking or not supportive for other autoimmune conditions. In this chapter, we present the main epidemiological findings that justify the conclusion that EBV is a component cause of MS and SLE and possible mechanisms underlying these effects. PMID:26424654

  1. Autoimmunity in 2015.

    PubMed

    Selmi, Carlo

    2016-08-01

    Compared to the clear trend observed in previous years, the number of peer-reviewed articles published during 2015 and retrieved using the "autoimmunity" key word declined by 4 %, while remaining 5 % of immunology articles. On the other hand, a more detailed analysis of the published articles in leading immunology and autoimmunity journals revealed exciting scenarios, with fascinating lines of evidence being supported by convincing data and likely followed by rapid translational or clinical developments. As examples, the study of the microbiome, the development of new serum or other tissue biomarkers, and a more solid understanding of disease pathogenesis and tolerance breakdown mechanisms have been central issues in the past year. Furthermore and similar to the oncology field, progress in the understanding of single autoimmune condition is becoming most specific with psoriatic and rheumatoid arthritis being ideal paradigms with treatment options diverging after decades of common therapies, as illustrated by IL17-targeting approaches. The ultimate result of these advances is towards personalized medicine with an ideal approach being tailored on a single patient, based on a finely tuned definition of the immunogenetics, epigenetics, microbiome, and biomarkers. Finally, experimental reports suggest that cancer-associated immune mechanisms or the role of T and B cell subpopulations should be better understood in autoimmune diseases. While we hailed the 2014 literature in the autoimmunity world as part of an annus mirabilis, we should not be mistaken in the strong stimulus of research in autoimmunity represented by the 2015 articles that will be summarized in this article. PMID:27422713

  2. [Autoimmune hemolytic anemia in children].

    PubMed

    Becheur, M; Bouslama, B; Slama, H; Toumi, N E H

    2015-01-01

    Autoimmune hemolytic anemia is a rare condition in children which differs from the adult form. It is defined by immune-mediated destruction of red blood cells caused by autoantibodies. Characteristics of the autoantibodies are responsible for the various clinical entities. Classifications of autoimmune hemolytic anemia include warm autoimmune hemolytic anemia, cold autoimmune hemolytic anemia, and paroxysmal cold hemoglobinuria. For each classification, this review discusses the epidemiology, etiology, clinical presentation, laboratory evaluation, and treatment options. PMID:26575109

  3. Things to Consider If You Have MG and Are Thinking about Getting Pregnant

    MedlinePlus

    ... diagnosis and optimal care of individuals affected by myasthenia gravis and closely related disorders and to improve their ... the authors, but not necessarily those of the Myasthenia Gravis Foundation of America (MGFA). Any reference to a ...

  4. Eyelid drooping

    MedlinePlus

    ... around or behind the eye Diabetes Horner syndrome Myasthenia gravis Stroke Swelling in the eyelid, such as ... performed include: Slit-lamp examination Tension test for myasthenia gravis Visual field testing

  5. Eyelid drooping

    MedlinePlus

    ... around or behind the eye Diabetes Horner syndrome Myasthenia gravis Stroke Swelling in the eyelid, such as ... performed include: Slit-lamp examination Tension test for myasthenia gravis Visual field testing Treatment If a disease ...

  6. Autoimmunity and Turner's syndrome.

    PubMed

    Lleo, Ana; Moroni, Luca; Caliari, Lisa; Invernizzi, Pietro

    2012-05-01

    Turner Syndrome (TS) is a common genetic disorder, affecting female individuals, resulting from the partial or complete absence of one sex chromosome, and occurring in approximately 50 per 100,000 liveborn girls. TS is associated with reduced adult height and with gonadal dysgenesis, leading to insufficient circulating levels of female sex steroids and to infertility. Morbidity and mortality are increased in TS but average intellectual performance is within the normal range. TS is closely associated to the presence of autoantibodies and autoimmune diseases (AID), especially autoimmune thyroiditis and inflammatory bowel disease. Despite the fact that the strong association between TS and AID is well known and has been widely studied, the underlying immunopathogenic mechanism remains partially unexplained. Recent studies have displayed how TS patients do not show an excess of immunogenic risk markers. This is evocative for a higher responsibility of X-chromosome abnormalities in the development of AID, and particularly of X-genes involved in immune response. For instance, the long arm of the X chromosome hosts a MHC-locus, so the loss of that region may lead to a deficiency in immune regulation. Currently no firm guidelines for diagnosis exist. In conclusion, TS is a condition associated with a number of autoimmune manifestations. Individuals with TS need life-long medical attention. As a consequence of these findings, early diagnosis and regular screening for potential associated autoimmune conditions are essential in the medical follow-up of TS patients. PMID:22154619

  7. Autoimmunity in Addison's disease.

    PubMed

    Martín Martorell, P; Roep, B O; Smit, J W A; Martorell, P M

    2002-08-01

    Addison's disease has a low incidence and is most frequently the result of an autoimmune disease in developed countries. Addison's disease can present as an isolated entity or in combination with other autoimmune diseases: Addison's disease can be part of the distinct polyglandular autoimmune syndromes APS I and II. Autoantibodies in patients with isolated Addison's disease are directed against the enzymes involved in steroid synthesis, P45oc21, P45oscc and P45oc17. Addison's disease, both isolated and in the context of APS II, has been associated with the haplotype HLA-A1, -B8 and DR3. The value of the increased expression of these molecules on adrenocortical cells could point towards an infectious pathogenesis. Given the prevalence, up to 80 %, of autoantibodies in Addison's disease as well as the high predictive value for developing the disease when antibodies are present (41% in three years), we advise screening high-risk populations, such as patients with other autoimmune endocrinopathies or their relatives for the presence of these antibodies. The adrenocortical function of patients positive for antibodies should be followed yearly. PMID:12430572

  8. [Polyglandular autoimmune syndromes : An overview].

    PubMed

    Komminoth, P

    2016-05-01

    Polyglandular autoimmune syndromes (PGAS), also known as autoimmune polyendocrinopathy syndromes (APS), are a heterogeneous group of rare, genetically caused diseases of the immune system which lead to inflammatory damage of various endocrine glands resulting in malfunctions. In addition, autoimmune diseases of non-endocrine organs may also be found. Early diagnosis of PGAS is often overlooked because of heterogeneous symptoms and the progressive occurrence of the individual diseases. The two most important forms of PGAS are the juvenile and adult types. The juvenile type (PGAS type 1) is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21, exhibits geographic variations in incidence and is defined by the combination of mucocutaneous candidiasis, Addison's disease and hypoparathyroidism. In addition, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome and other autoimmune diseases can also occur. The adult form of PGAS (PGAS type 2) is a multigenetic disorder associated with some HLA haplotypes, is more common than the juvenile type, shows female predominance and exhibits the combination of type 1 diabetes, autoimmune thyroid disease, Addison's disease and other autoimmune disorders. The histological alterations in affected organs of PGAS patients are similar to findings in sporadically occurring autoimmune diseases of these organs but there are no pathognomic fine tissue findings. If patients exhibit autoimmune changes in two different endocrine glands or if there are indications of several autoimmune disorders from the patient history, it is important to consider PGAS and inform the clinicians of this suspicion. PMID:27099223

  9. [Autoimmune hemolytic anemia].

    PubMed

    Karasawa, Masamitsu

    2008-03-01

    Diagnosis of autoimmune hemolytic anemia (AIHA) requires both serologic evidence of an autoantibody and hemolysis. Based on the characteristic temperature reactivity of the autoantibody to red cell membranes, AIHA is classified into warm AIHA or cold AIHA (cold agglutinin disease and paroxysmal cold hemoglobinuria). Sensitized RBCs are destructed by intravascular and/or extravascular hemolysis. On the basis of etiology, AIHA are classified as idiopathic or secondary. The common cause of secondary AIHA is lymphoproliferative disorders, autoimmune diseases, and infections. The first line therapy of patients with warm AIHA is glucocorticoids and primary treatment for cold AIHA is avoiding cold exposure. The other standard treatments include splenectomy and immunosuppressive drugs. Recently, rituximab, a monoclonal anti-CD20 antibody, has been used in refractory AIHA with excellent responses. PMID:18326320

  10. Postoperative survival for patients with thymoma complicating myasthenia gravis—preliminary retrospective results of the ChART database

    PubMed Central

    Wang, Fangrui; Fu, Jianhua; Shen, Yi; Wei, Yucheng; Tan, Lijie; Zhang, Peng; Han, Yongtao; Chen, Chun; Zhang, Renquan; Li, Yin; Chen, Keneng; Chen, Hezhong; Liu, Yongyu; Cui, Youbing; Wang, Yun; Yu, Zhentao; Zhou, Xinming; Liu, Yangchun; Liu, Yuan; Gu, Zhitao

    2016-01-01

    Background It is so far not clear that how myasthenia gravis (MG) affected the prognosis of thymoma patients. The aim of this assay is to compare the postoperative survival between patients with thymoma only and those with both thymoma and MG. Methods The Chinese Alliance for Research in Thymomas (ChART) registry recruited patients with thymoma from 18 centers over the country on an intention to treat basis from 1992 to 2012. Two groups were formed according to whether the patient complicated MG. Demographic and clinical data were reviewed, patients were followed and their survival status were analyzed. Results There were 1,850 patients included in this study, including 421 with and 1,429 without MG. Complete thymectomy were done in 91.2% patients in MG group and 71.0% in non-MG group (P<0.05). There were more percentage of patients with the histology of thymoma AB, B1, or B2 (P<0.05) in MG group, and more percentage of patients with MG were in Masaoka stage I and II. The 5- and 10-year overall survival (OS) rates were both higher in MG group (93% vs. 88%; 83% vs. 81%, P=0.034) respectively. The survival rate was significantly higher in patients with MG when the Masaoka staging was 3/4 (P=0.003). Among patients with advanced stage thymoma (stage 3, 4a, 4b), the constituent ratios of 3, 4a, 4b were similar between MG and non-MG group. Histologically, however, there were significantly more proportion of AB/B1/B2/B3 in the MG group while there were more C in the non-MG group (P=0.000). Univariate analyses for all patients showed that MG, WHO classification, Masaoka stage, surgical approach, chemotherapy and radiotherapy and resectability were significant factors, and multivariate analysis showed WHO classification, Masaoka stage, and resectability were strong independent prognostic indicators. Conclusions Although MG is not an independent prognostic factor, the survival of patients with thymoma was superior when MG was present, especially in late Masaoka stage

  11. Passive and active immunization models of MuSK-Ab positive myasthenia: electrophysiological evidence for pre and postsynaptic defects.

    PubMed

    Viegas, Stuart; Jacobson, Leslie; Waters, Patrick; Cossins, Judith; Jacob, Saiju; Leite, M Isabel; Webster, Richard; Vincent, Angela

    2012-04-01

    Antibodies directed against the post-synaptic neuromuscular junction protein, muscle specific kinase (MuSK) are found in a small proportion of generalized myasthenia gravis (MuSK-MG) patients. MuSK is a receptor tyrosine kinase which is essential for clustering of the acetylcholine receptors (AChRs) at the neuromuscular junction, but the mechanisms by which MuSK antibodies (MuSK-Abs) affect neuromuscular transmission are not clear. Experimental models of MuSK-MG have been described but there have been no detailed electrophysiological studies and no comparisons between the MuSK-MG and the typical form with AChR-Abs (AChR-MG). Here we studied the electrophysiology of neuromuscular transmission after immunization against MuSK compared with immunization against AChR, and also after passive transfer of IgG from MuSK-MG or AChR-MG patients. Overt clinical weakness was observed in 6/10 MuSK-immunized and 3/9 AChR-immunized mice but not in those injected with patients' IgG. Miniature endplate potentials (MEPPS) were reduced in all weak mice consistent with the reduction in postsynaptic AChRs that was found. However, whereas there was an increase in the quantal release of acetylcholine (ACh) in the weak AChR-immunized mice, no such increase was found in the weak MuSK-immunized mice. Similar trends were found after the passive transfer of purified IgG antibodies from MuSK-MG or AChR-MG patients. Preliminary results showed that MuSK expression was considerably higher at the neuromuscular junctions of the masseter (facial) than in the gastrocnemius (leg) with no reduction in MuSK immunostaining at the neuromuscular junctions. Overall, these results suggest that MuSK antibodies act in at least two ways. Firstly by indirectly affecting MuSK's ability to maintain the high density of AChRs and secondly by interfering with a compensatory presynaptic mechanism that regulates quantal release and helps to preserve neuromuscular function. These results raise questions about how MuSK is

  12. Cytokines and autoimmunity.

    PubMed Central

    Cavallo, M G; Pozzilli, P; Thorpe, R

    1994-01-01

    Although the immunopathology of most autoimmune diseases has been well defined, the mechanisms responsible for the breakdown of self-tolerance and which lead to the development of systemic and organ-specific autoaggression are still unclear. Evidence has accumulated which supports a role for a disregulated production of cytokines by leucocytes and possibly other cells in the pathogenesis of some autoimmune diseases. However, due to the complexity and heterogeneity of cytokine effects in the regulation of the immune response, it is difficult to determine whether abnormalities in the patterns of cytokine production are primary or secondary to the pathological process. Confusion is also caused by the fact that the biological activities of cytokines are multiple and often overlapping, and consequently it is difficult to focus on a unique effect of any one cytokine. Characterization of the potential and actual involvement of cytokines is important not only for a better understanding of the pathogenesis of autoimmune conditions, but particularly because of the implications for the development of immunotherapeutic strategies for the prevention and treatment of the diseases. PMID:8149655

  13. Autoimmune mechanisms in psoriasis.

    PubMed

    Reeves, W H

    1991-09-01

    Psoriasis is a chronic papulosquamous skin disorder affecting 1% to 3% of the general population. There is increasing evidence that immunologic mechanisms are involved in the pathogenesis of psoriasis, and that a link between psoriasis and autoimmunity may exist. A variety of autoantibodies has been observed in psoriasis including antinuclear antibodies, antibodies to small nuclear and cytoplasmic ribonucleoproteins, and antibodies to epidermal cells. UV light treatment of psoriasis may play a role in inducing these autoantibodies in some individuals. Recent evidence that activated T cells in psoriatic plaques may produce interferon-gamma leading to the appearance of ectopic class II major histocompatibility products on the surface of keratinocytes also supports the idea of a link between psoriasis and disordered immunoregulation. The immunologic abnormalities in psoriasis and the association of psoriasis with particular types of autoantibodies raise the possibility that a common etiology may underlie both psoriasis and autoimmunity in some patients, but the different responses of the two diseases to UV light treatment and certain pharmacological agents suggest that psoriasis may not have an autoimmune pathogenesis. PMID:1931571

  14. Autoantibodies in Autoimmune Pancreatitis

    PubMed Central

    Smyk, Daniel S.; Rigopoulou, Eirini I.; Koutsoumpas, Andreas L.; Kriese, Stephen; Burroughs, Andrew K.; Bogdanos, Dimitrios P.

    2012-01-01

    Autoimmune pancreatitis (AIP) was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA) positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis. PMID:22844291

  15. Age dependent course of EAE in Aire-/- mice.

    PubMed

    Aharoni, Rina; Aricha, Revital; Eilam, Raya; From, Ido; Mizrahi, Keren; Arnon, Ruth; Souroujon, Miriam C; Fuchs, Sara

    2013-09-15

    This study explores the consequences of deficiency in the autoimmune regulator (Aire) on the susceptibility to experimental autoimmune encephalomyelitis (EAE). Increased susceptibility to EAE was found in Aire knockout (KO) compared to wild type (WT) in 6month old mice. In contrast, 2month old Aire KO mice were less susceptible to EAE than WT mice, and this age-related resistance correlated with elevated proportions of T regulatory (Treg) cells in their spleen and brain. Combined with our previous findings in experimental autoimmune myasthenia gravis, we suggest an age-related association between Aire and Treg cells in the susceptibility to autoimmunity. PMID:23849800

  16. The spectrum of autoimmune encephalopathies.

    PubMed

    Dubey, Divyanshu; Sawhney, Anshudha; Greenberg, Benjamin; Lowden, Andrea; Warnack, Worthy; Khemani, Pravin; Stuve, Olaf; Vernino, Steven

    2015-10-15

    Despite being a potentially reversible neurological condition, no clear guidelines for diagnosis or management of autoimmune encephalitis exist. In this study we analyzed clinical presentation, laboratory and imaging characteristics, and outcome of autoimmune encephalitis from three teaching hospitals. Non-paraneoplastic autoimmune encephalitis associated with antibodies against membrane antigens was the most common syndrome, especially in the pediatric population. Clinical outcome was better for patients with shorter latency from symptom onset to diagnosis and initiation of immunomodulation. Patients with underlying malignancy were less likely to respond well to immunomodulatory therapy. The clinical spectrum of autoimmune encephalitis is fairly broad, but prompt recognition and treatment often leads to excellent outcome. PMID:26439968

  17. Myasthenic syndromes.

    PubMed

    Farrugia, M E

    2011-03-01

    The neuromuscular junction is vulnerable to autoimmune attack both at the pre-synaptic nerve terminal and at the post-synaptic muscle membrane. Antibodies directed to the nicotinic acetylcholine receptor at the muscle surface are the cause of myasthenia gravis in the majority of cases. Myasthenia gravis is an acquired condition, characterised by weakness and fatigability of the skeletal muscles. The ocular muscles are commonly affected first, but the disease often generalises. Treatment includes symptom control and immunosuppression. The thymus gland plays an important role in the pathogenesis of myasthenia gravis and thymectomy is indicated in certain subgroups. Lambert-Eaton myasthenic syndrome is associated with antibodies directed to the voltage-gated calcium channel antibodies at the pre-synaptic nerve terminal. It is an acquired condition and, in some cases, may be paraneoplastic, often secondary to underlying small cell lung carcinoma. Clinical presentation is distinct from myasthenia gravis, with patients often first presenting with lower limb muscle fatigability and autonomic symptoms. Congenital myasthenic syndromes are inherited neuromuscular disorders due to mutations in proteins at the neuromuscular junction. Various phenotypes exist depending on the protein mutation. Treatment is directed towards symptom control and immunosuppression is not indicated. PMID:21365067

  18. Autoimmune diseases and myelodysplastic syndromes.

    PubMed

    Komrokji, Rami S; Kulasekararaj, Austin; Al Ali, Najla H; Kordasti, Shahram; Bart-Smith, Emily; Craig, Benjamin M; Padron, Eric; Zhang, Ling; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; List, Alan F; Mufti, Ghulam J; Epling-Burnette, Pearlie K

    2016-05-01

    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation. PMID:26875020

  19. Autoimmune muscle disease.

    PubMed

    Mammen, Andrew

    2016-01-01

    Patients with polymyositis (PM), dermatomyositis (DM), and immune-mediated necrotizing myopathy (IMNM) present with the subacute onset of symmetric proximal muscle weakness, elevated muscle enzymes, myopathic findings on electromyography, and autoantibodies. DM patients are distinguished by their cutaneous manifestations. Characteristic features on muscle biopsy include the invasion of nonnecrotic muscle fibers by T cells in PM, perifascicular atrophy in DM, and myofiber necrosis without prominent inflammation in IMNM. Importantly, these are regarded as autoimmune diseases and most patients respond partially, if not completely, to immunosuppressive therapy. Patients with inclusion body myositis (IBM) usually present with the insidious onset of asymmetric weakness in distal muscles (e.g., wrist flexors, and distal finger flexors), often when more proximal muscle groups are relatively preserved. Although IBM muscle biopsies usually have focal invasion of myofibers by lymphocytes, the majority of IBM biopsies also include rimmed vacuoles. While most IBM patients do have autoantibodies, treatment with immunosuppressive agents does not improve their clinical course. Along with the presence of abnormally aggregated proteins on muscle biopsy, the refractory nature and relentless course of IBM suggest that the underlying pathophysiology may include a dominant myodegenerative component. This chapter will focus on the epidemiology, clinical presentation, and treatment of the autoimmune myopathies and IBM. An emphasis will be placed on recent advances, indicating that these are a diverse family of diseases and that each of more than a dozen myositis autoantibodies is associated with a distinct clinical phenotype. PMID:27112692

  20. [Autoimmune lymphoproliferative syndrome].

    PubMed

    Rodrigues, Vera; Conde, Marta; Figueiredo, António; Vasconcelos, Júlia; Dias, Alexandra

    2011-01-01

    The Autoimmune Lymphoproliferative Syndrome (ALPS) is an impairment of lymphocyte apoptosis expressed by generalized non-malignant lymphoproliferation, lymphadenopathy and/or splenomegaly. This article describes a seven and 14 year old males. The first one was admitted at 3 years of age with fever, bicytopenia and generalized lymphadenopathy. Hystopathological analysis of lymph nodes showed reactive follicular hyperplasia and marked paracortical expansion. He was readmitted three years later presenting herpes zoster and similar clinical features. High levels of IL-10 and increasing tendency of Fas-L in plasma and serum. The second child was admitted at 13 years of age presenting thigh and gluteus cellulitis, anemia and neutropenia. T lymphocytes aß+CD4-CD8- 3,1%. Hystopathological analysis of lymph nodes showed marked paracortical hyperplasia. Both children are treated with mycophenolate mofetil with good response. ALPS is an underestimated entity that must be considered in non malign lymphoproliferation, autoimmunity and expansion of an unusual population of a/ßCD3+CD4-CD8-(double-negative T cells>1%). PMID:22525637

  1. [Hydroxychloroquine for autoimmune diseases].

    PubMed

    Danza, Álvaro; Graña, Diego; Goñi, Mabel; Vargas, Andrea; Ruiz-Irastorza, Guillermo

    2016-02-01

    Hydroxychloroquine (HCQ) is by far the most frequently used antimalarial for the management of Systemic Autoimmune Diseases. It has immunomodulatory, hypolipidemic, hypoglycemic and antithrombotic properties and it diminishes the risk of malignancies. The most important mechanisms to explain the immunomodulatory actions are its ability to reduce inflammatory pathways and Toll-like receptors activation. The safety profile is favorable. In spite of its low frequency, retinal toxicity is potentially severe. In systemic lupus erythematous HCQ therapy reduces activity, the accrual of organ damage, risk of infections and thrombosis and improves the cardiometabolic profile. It contributes to induce lupus nephritis remission, spares steroid use and increases survival rates. In rheumatoid arthritis, it improves cardiometabolic risk and has a favorable effect in joint inflammation. In Sjögren's syndrome, an increased lacrimal quality as well as an improvement in objective and subjective inflammatory markers has been demonstrated with HCQ. In Antiphospholipid Syndrome, HCQ is effective in primary and secondary thrombosis prevention. The effectiveness of the drug in other systemic autoimmune diseases is less established. HCQ therapy may improve dermatological manifestations in Dermatomyositis and may have a positive effects in the treatment of Sarcoidosis and Still disease. PMID:27092678

  2. Aquaporin-4 autoimmunity

    PubMed Central

    Zekeridou, Anastasia

    2015-01-01

    Neuromyelitis optica (NMO) and a related spectrum of inflammatory CNS disorders are unified by detection of a serum autoantibody specific for the aquaporin-4 (AQP4) water channel, which is abundant in astrocytic foot processes. The classic clinical manifestations of NMO are optic neuritis and longitudinally extensive transverse myelitis. Newly recognized manifestations of AQP4 autoimmunity include lesions of circumventricular organs and skeletal muscle. NMO is commonly relapsing, is frequently accompanied by other autoimmune disorders, and sometimes occurs in a paraneoplastic context. The goals of treatment are to minimize neurologic disability in the acute attack and thereafter to prevent relapses and cumulative disability. The disease specificity of AQP4 immunoglobulin (Ig) G approaches 100% using optimized molecular-based detection assays. Clinical, immunohistopathologic, and in vitro evidence support this antibody being central to NMO pathogenesis. Current animal models yield limited histopathologic characteristics of NMO, with no clinical deficits to date. Recent descriptions of a myelin oligodendrocyte glycoprotein autoantibody in a minority of patients with NMO spectrum phenotype who lack AQP4-IgG predict serologic delineation of additional distinctive disease entities. PMID:26185772

  3. Environmental Triggers of Autoimmune Thyroiditis

    PubMed Central

    Burek, C. Lynne; Talor, Monica V.

    2009-01-01

    Autoimmune thyroiditis is among the most prevalent of all the autoimmunities. Autoimmune thyroiditis is multifactorial with contributions from genetic and environmental factors. Much information has been published about the genetic predisposition to autoimmune thyroiditis both in experimental animals and humans. There is, in contrast, very little data on environmental agents that can serve as the trigger or autoimmunity in a genetically predisposed host. The best-established environmental factor is excess dietary iodine. Increased iodine consumption is strongly implicated as a trigger for thyroiditis, but only in genetically susceptible individuals. However, excess iodine is not the only environmental agent implicated as a trigger leading to autoimmune thyroiditis. There are a wide variety of other synthetic chemicals that affect the thyroid gland or have the ability to promote immune dysfunction in the host. These chemicals are released into the environment by design, such as in pesticides, or as a by-product of industry. Candidate pollutants include polyaromatic hydrocarbons, polybrominated biphenols, and polychlorinated biphenols, among others. Infections are also reputed to trigger autoimmunity and may act alone or in concert with environmental chemicals. We have utilized a unique animal model, the NOD.H2h4 mouse to explore the influence of iodine and other environmental factors on autoimmune thyroiditis. PMID:19818584

  4. Environmental triggers of autoimmune thyroiditis.

    PubMed

    Burek, C Lynne; Talor, Monica V

    2009-01-01

    Autoimmune thyroiditis is among the most prevalent of all the autoimmunities. Autoimmune thyroiditis is multifactorial with contributions from genetic and environmental factors. Much information has been published about the genetic predisposition to autoimmune thyroiditis both in experimental animals and humans. There is, in contrast, very little data on environmental agents that can serve as the trigger for autoimmunity in a genetically predisposed host. The best-established environmental factor is excess dietary iodine. Increased iodine consumption is strongly implicated as a trigger for thyroiditis, but only in genetically susceptible individuals. However, excess iodine is not the only environmental agent implicated as a trigger leading to autoimmune thyroiditis. There are a wide variety of other synthetic chemicals that affect the thyroid gland or have the ability to promote immune dysfunction in the host. These chemicals are released into the environment by design, such as in pesticides, or as a by-product of industry. Candidate pollutants include polyaromatic hydrocarbons, polybrominated biphenols, and polychlorinated biphenols, among others. Infections are also reputed to trigger autoimmunity and may act alone or in concert with environmental chemicals. We have utilized a unique animal model, the NOD.H2(h4) mouse to explore the influence of iodine and other environmental factors on autoimmune thyroiditis. PMID:19818584

  5. Mast Cell and Autoimmune Diseases

    PubMed Central

    Xu, Yunzhi; Chen, Guangjie

    2015-01-01

    Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases. PMID:25944979

  6. Autoimmunity in neuromuscular disease.

    PubMed

    Newsom-Davis, J

    1988-01-01

    A number of confounding factors can be identified from the search for autoimmune mechanisms over the last 2 decades that may be relevant for future studies. (1) An apparently homogeneous clinical disorder may represent more than one disease process and thereby imply antibody/antigen heterogeneity as, for example, in MG with and without detectable anti-AChR antibodies. In some cases, physiologic studies allow the different forms of the disease to be distinguished as in AIDP and acute inflammatory axonal polyneuropathy. (2) A homogeneous disorder (e.g., LEMS) may have at least two different triggering mechanisms (SCLC and an unknown stimulus). (3) Antigen density may be too low to be detected by the immunohistologic techniques available, as initially occurred in MG and LEMS. (4) Autoantibodies may be detected that are irrelevant to the primary disease, such as anti-striated muscle antibodies in MG. (5) Poor antibody cross-reactivity between species may mean that the pathogenic antibody is undetected in binding assays or in experimental passive transfer studies. For example, anti-AChR antibody in MG shows less than 5% reactivity with Torpedo AChR. (6) A poor regenerative capacity of the target antigen may mean that reduction of circulating autoantibodies by either plasma exchange or ISD treatment is not associated with detectable clinical improvement, as may be the case in SSN in which DRG cells appear to be the target. TABLE 5 summarizes the extent to which the data reviewed have established a role for pathogenic antibodies in the light of the postulates for autoimmunity set out earlier and ranks the disorders accordingly. Only in MG with detectable anti-AChR antibody are all the postulates met, including definition of the antigen, experimental passive transfer by the IgG fraction of MG sera, active immunization of experimental animals, and propagation. In both LEMS and the IgM kappa anti-MAG demyelinating neuropathy the antigen is known, although better

  7. Autoimmune hemolytic anemia.

    PubMed

    Dacie, J V

    1975-10-01

    Warm-type autoantibodies of autoimmune hemolytic anemia (AIHA) are usually IgG but may be IgM or IgA. They are usual Rh specific. Cold-type antibodies are IgM or IgG (Donath-Landsteiner [DL] antibody). IgM antibodies are usually anit-l (occasionally anti-i) and DL antibodies anti-P. The warm IgG antibodies do not fix complement (C); they cause red blood cell (RBC) destruction predominantly in the spleen as the result of interaction between fixing; they cause RBC destruction either by intravascular lysis (complement sequence completed) or by interaction between C3-coated RBCs and phagocytes in liver and spleen. Gentic factors, immunoglobulin deficiency, somatic mutation, viral infections and drugs, and failure of T-lymphocyte function, all probably play a part in breaking immunological tolerance and the development of AIHA. PMID:1164110

  8. Update on Autoimmune Hepatitis

    PubMed Central

    Liberal, Rodrigo; Vergani, Diego; Mieli-Vergani, Giorgina

    2015-01-01

    Autoimmune hepatitis (AIH), a liver disorder affecting both children and adults, is characterized by inflammatory liver histology, elevated transaminase levels, circulating nonorganspecific autoantibodies, and increased levels of immunoglobulin G, in the absence of a known etiology. Two types of AIH are recognized according to seropositivity: smooth muscle antibody and/or antinuclear antibody define AIH type 1 and antibodies to liver-kidney microsome type 1 and/or liver cytosol type 1 define AIH type 2. AIH type 1 affects both adults and children, while AIH type 2 is mainly a paediatric disease, though it does occasionally affects young adults. AIH should be considered during the diagnostic workup of any patient with increased liver enzyme levels. AIH is exquisitely responsive to immunosuppressive treatment with prednisolone with or without azathioprine, with symptom free long-term survival for the majority of patients. For those who do not respond to standard treatment, or who are difficult-to-treat, mycophenolate mofetil and, in the absence of a response, calcineurin inhibitors should be tried in addition to steroids. The pathogenesis of AIH is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4 T-cells, although recent studies support the involvement of diverse populations, including Th17 cells. A deeper understanding of the pathogenesis of AIH is likely to contribute to the development of novel treatments, such as the adoptive transfer of autologous expanded antigenspecific regulatory T-cells, which ultimately aim at restoring tolerance to liver-derived antigens. PMID:26357634

  9. Type 1 diabetes associated autoimmunity.

    PubMed

    Kahaly, George J; Hansen, Martin P

    2016-07-01

    Diabetes mellitus is increasing in prevalence worldwide. The economic costs are considerable given the cardiovascular complications and co-morbidities that it may entail. Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the loss of insulin-producing pancreatic β-cells. The pathogenesis of T1D is complex and multifactorial and involves a genetic susceptibility that predisposes to abnormal immune responses in the presence of ill-defined environmental insults to the pancreatic islets. Genetic background may affect the risk for autoimmune disease and patients with T1D exhibit an increased risk of other autoimmune disorders such as autoimmune thyroid disease, Addison's disease, autoimmune gastritis, coeliac disease and vitiligo. Approximately 20%-25% of patients with T1D have thyroid antibodies, and up to 50% of such patients progress to clinical autoimmune thyroid disease. Approximately 0.5% of diabetic patients have concomitant Addison's disease and 4% have coeliac disease. The prevalence of autoimmune gastritis and pernicious anemia is 5% to 10% and 2.6% to 4%, respectively. Early detection of antibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown disease. Patients and family members should be educated to be able to recognize signs and symptoms of underlying disease. PMID:26903475

  10. Immunisation with Torpedo acetylcholine receptor.

    PubMed

    Elfman, L

    1984-01-01

    Acetylcholine mediates the transfer of information between neurons in the electric organ of, for example, Torpedo as well as in vertebrate skeletal muscle. The nicotinic acetylcholine receptor complex translates the binding of acetylcholine into ion permeability changes. This leads to an action potential in the muscle fibre. The nicotinic acetylcholine receptor protein has been purified from Torpedo by use of affinity chromatography. The receptor is an intrinsic membrane glycoprotein composed of five polypeptide chains. When various animals are immunised with the receptor they demonstrate clinical signs of severe muscle weakness coincident with high antibody titres in their sera. The symptoms resemble those found in the autoimmune neuromuscular disease myasthenia gravis in humans. This animal model has constituted a unique model for studying autoimmune diseases. This paper reviews some of the work using Torpedo acetylcholine receptor in order to increase the understanding of the motor nervous system function and myasthenia gravis. It is now known that the nicotinic acetylcholine receptor protein is the antigen involved in myasthenia gravis. The mechanism of immune damage involves a direct block of the receptor function. This depends on the presence of antibodies which crosslink the postsynaptic receptors leading to their degradation. The questions to be answered in the future are; (a) what initiates or triggers the autoimmune response, (b) how do the antibodies cause the symptoms--is there a steric hindrance of the interaction of acetylcholine and the receptor, (c) why is there not a strict relationship between antibody titre and severity of symptoms, and (d) why are some muscles affected and other spared? With help of the experimental model, answers to these questions may result in improved strategies for the treatment of the autoimmune disease myasthenia gravis. PMID:6097937

  11. Questions and Answers on Autoimmunity and Autoimmune Diseases

    MedlinePlus

    ... for Updates Join Our Email List For Email Marketing you can trust. Contact AARDA National Office 22100 ... Grassroots Fundraising Workplace Giving Special Events AARDA on Facebook Copyright © 2004 - 2016. American Autoimmune Related Diseases Association, ...

  12. Sensory Neuronopathy and Autoimmune Diseases

    PubMed Central

    Martinez, Alberto R. M.; Nunes, Marcelo B.; Nucci, Anamarli; França, Marcondes C.

    2012-01-01

    Sensory neuronopathies (SNs) are a specific subgroup of peripheral nervous system diseases characterized by primary degeneration of dorsal root ganglia and their projections. Multifocal sensory symptoms often associated to ataxia are the classical features of SN. Several different etiologies have been described for SNs, but immune-mediated damage plays a key role in most cases. SN may herald the onset of some systemic autoimmune diseases, which further emphasizes how important the recognition of SN is in clinical practice. We have thus reviewed available clinical, neurophysiological, and therapeutic data on autoimmune disease-related SN, namely, in patients with Sjögren's syndrome, autoimmune hepatitis, and celiac disease. PMID:22312482

  13. Autoimmune Thyroid Diseases in Children

    PubMed Central

    Cappa, Marco; Bizzarri, Carla; Crea, Francesca

    2011-01-01

    The two major autoimmune thyroid diseases (ATDs) include Graves' disease (GD) and autoimmune thyroiditis (AT); both of which are characterized by infiltration of the thyroid by T and B cells reactive to thyroid antigens, by the production of thyroid autoantibodies and by abnormal thyroid function (hyperthyroidism in GD and hypothyroidism in AT). While the exact etiology of thyroid autoimmunity is not known, it is believed to develop when a combination of genetic susceptibility and environmental encounters leads to breakdown of tolerance. It is important to recognize thyroid dysfunction at an early stage by maintaining an appropriate index of suspicion. PMID:21209713

  14. [Autoimmune pancreatitis as an element of autoimmune polyglandular syndrome].

    PubMed

    Dyrla, Przemysław; Nowak, Tomasz; Gil, Jerzy; Adamiec, Cezary; Bobula, Mariusz; Saracyn, Marek

    2016-05-26

    Autoimmune pancreatitis constantly belongs to diseases which often causes significant diagnostic problem and often runs out with surgical intervention as considered to be a pancreatic cancer. Important although usually underestimated problems are polyglandular syndromes, which may consist of autoimmune pancreatitis (AIP) problem as well. This case report is an example of autoimmune polyglandular syndrome (APS), which was connected with the surgical treatment with biliary bypass anastomosis because of the unresectable lesion in the head of pancreas. The definite remission of the pancreatic lesion finally came after a steroid therapy. Differentiation between neoplastic and inflammatory pancreatic tumors very often remains a serious clinical problem. On grounds of imaging and cytopathology exams it is often difficult to decide about the nature of a lesion. The negative result of cytopathological biopsy examination does not finally settle straightforward diagnosis. Diagnostic problems affect also autoimmune pancreatitis. It is worth to undertake attempts to differentiate pancreatic lesions especially in cases of concomitance with other autoimmune polyglandular syndromes. That is because it is connected with completely different treatment and outcome. We should remember about diagnostic criteria of autoimmune pancreatitis. Appropriate diagnosis for patients with AIP gives them a chance to avoid serious surgical resection and possible complications. PMID:27234865

  15. [Molecular diagnosis of autoimmune dermatoses].

    PubMed

    Hoffmann, K; Hertl, M; Sitaru, C

    2016-01-01

    Bullous autoimmune diseases are organ-specific disorders characterized by an autoantibody-mediated blistering of skin and mucous membranes. The detection of tissue-bound and serum autoantibodies is prerequisite for the diagnosis of autoimmune blistering diseases. The individual entities of this group may be difficult to differentiate on clinical grounds alone. An accurate diagnosis is however important for prognosis and therapy. A preliminary diagnostic step includes direct and indirect immunofluorescence microscopy, which provide information about the binding pattern and isotype of autoantibodies and allow the diagnosis of the autoimmune blistering disease. Subsequent characterization of the molecular specificity of autoantibodies is necessary for the exact classification of autoimmune bullous dermatoses. The quantitative measurement of autoantibodies against structural proteins of the skin may be often used to assess disease severity at follow-up. PMID:26612472

  16. Epigenetic alterations underlying autoimmune diseases.

    PubMed

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein

    2016-03-01

    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases. PMID:26761426

  17. American Autoimmune Related Diseases Association

    MedlinePlus

    ... Statistics Your source for autoimmune related disease information. **We need your input** We want to know of your experiences with Non- ... email address with us. Please be assured that we will always keep your email private. We will ...

  18. Sialic acids and autoimmune disease.

    PubMed

    Mahajan, Vinay S; Pillai, Shiv

    2016-01-01

    An important underlying mechanism that contributes to autoimmunity is the loss of inhibitory signaling in the immune system. Sialic acid-recognizing Ig superfamily lectins or Siglecs are a family of cell surface proteins largely expressed in hematopoietic cells. The majority of Siglecs are inhibitory receptors expressed in immune cells that bind to sialic acid-containing ligands and recruit SH2-domain-containing tyrosine phosphatases to their cytoplasmic tails. They deliver inhibitory signals that can contribute to the constraining of immune cells, and thus protect the host from autoimmunity. The inhibitory functions of CD22/Siglec-2 and Siglec-G and their contributions to tolerance and autoimmunity, primarily in the B lymphocyte context, are considered in some detail in this review. The relevance to autoimmunity and unregulated inflammation of modified sialic acids, enzymes that modify sialic acid, and other sialic acid-binding proteins are also reviewed. PMID:26683151

  19. Autoimmune sleep disorders.

    PubMed

    Silber, Michael H

    2016-01-01

    A number of autoantibodies, some paraneoplastic, are associated with sleep disorders. Morvan syndrome and limbic encephalitis, associated with voltage-gated potassium channel-complex antibodies, principally against CASPR2 and LGI1, can result in profound insomnia and rapid eye movement sleep behavior disorder (RBD). Patients with aquaporin-4 antibodies and neuromyelitis optica may develop narcolepsy in association with other evidence of hypothalamic dysfunction, sometimes as the initial presentation. Central sleep apnea and central neurogenic hypoventilation are found in patients with anti-N-methyl-d-aspartate receptor antibody encephalitis, and obstructive sleep apnea, stridor, and hypoventilation are prominent features of a novel tauopathy associated with IgLON5 antibodies. In addition, paraneoplastic diseases may involve the hypothalamus and cause sleep disorders, particularly narcolepsy and RBD in those with Ma1 and Ma2 antibodies. Patients with antineuronal nuclear autoantibodies type 2 may develop stridor. Several lines of evidence suggest that narcolepsy is an autoimmune disorder. There is a strong relationship with the human leukocyte antigen (HLA) DQB1*06:02 haplotype and polymorphisms in the T-cell receptor alpha locus and purinergic receptor P2Y11 genes. Patients with recent-onset narcolepsy may have high titers of antistreptococcal or other antibodies, although none has yet been shown to be disease-specific but, supporting an immune basis, recent evidence indicates that narcolepsy in children can be precipitated by one type of vaccination against the 2009-2010 H1N1 influenza pandemic. PMID:27112685

  20. Autoimmune and inflammatory epilepsies.

    PubMed

    Nabbout, Rima

    2012-09-01

    The role of immunity and inflammation in epilepsy have long been suggested by the anticonvulsant activity of steroids in some infancy and childhood epilepsies. The role of fever and infection in exacerbating seizures due to possible proinflammatory molecules, the increased frequency of seizures in systemic autoimmune diseases like systemic lupus erythematous, and, recently, the detection of autoantibodies in some unexplained epilepsies reinforced the causal place of immunity and inflammation in epilepsies with unknown etiology. In this article, we summarize epilepsies where clinical and biologic data strongly support the pathogenic role of autoantibodies (e.g., limbic encephalitides, N-methyl-d-aspartate [NMDA] encephalitis) and epilepsies where immune-mediated inflammation occurs, but the full pathogenic cascade is either not clear (e.g., Rasmussen's encephalitis) or only strongly hypothesized (idiopathic hemiconvulsion-hemiplegia syndrome [IHHS] and fever-induced refractory epilepsy in school-aged children [FIRES]). We emphasize the electroclinical features that would help to diagnose these conditions, allowing early immunomodulating therapy. Finally, we raise some questions that remain unclear regarding diagnosis, mechanisms, and future therapies. PMID:22946722

  1. Progesterone and Autoimmune Disease

    PubMed Central

    Hughes, Grant C.

    2011-01-01

    Sexual dimorphism in human immune systems is most apparent in the female predominance of certain autoimmune diseases (ADs) like systemic lupus erythematosus (SLE). Epidemiologic, observational and experimental evidence strongly suggest sex steroids are important modulators of genetic risk in human AD. In this regard, the roles of progesterone (Pg), an immunomodulatory female sex steroid, are poorly understood. Several lines of investigation indicate Pg and synthetic progestins impact risk of AD and immune-mediated injury in different ways depending on their concentrations and their engagement of various Pg receptors expressed in immune organs, immune cells or tissues targeted by immune attack. At low physiologic levels, Pg may enhance interferon-alpha (IFN-α) pathways important in SLE pathogenesis. Commonly used synthetic progestins may have the opposite effect. At pregnancy levels, Pg may suppress disease activity in rheumatoid arthritis (RA) and multiple sclerosis (MS) via inhibition of T helper type 1 (Th1) and Th17 pathways and induction of anti-inflammatory molecules. Importantly, Pg’s immunomodulatory effects differ from those of estrogens and androgens. An additional layer of complexity arises from apparent interdependence of sex hormone signaling pathways. Identifying mechanisms by which Pg and other sex steroids modulate risk of AD and immune-mediated injury will require clarification of their cellular and molecular targets in vivo. These future studies should be informed by recent genetic discoveries in human AD, particularly those revealing their sex-specific genetic associations. PMID:22193289

  2. Heparanase and Autoimmune Diabetes

    PubMed Central

    Simeonovic, Charmaine J.; Ziolkowski, Andrew F.; Wu, Zuopeng; Choong, Fui Jiun; Freeman, Craig; Parish, Christopher R.

    2013-01-01

    Heparanase (Hpse) is the only known mammalian endo-β-d-glucuronidase that degrades the glycosaminoglycan heparan sulfate (HS), found attached to the core proteins of heparan sulfate proteoglycans (HSPGs). Hpse plays a homeostatic role in regulating the turnover of cell-associated HS and also degrades extracellular HS in basement membranes (BMs) and the extracellular matrix (ECM), where HSPGs function as a barrier to cell migration. Secreted Hpse is harnessed by leukocytes to facilitate their migration from the blood to sites of inflammation. In the non-obese diabetic (NOD) model of autoimmune Type 1 diabetes (T1D), Hpse is also used by insulitis leukocytes to solubilize the islet BM to enable intra-islet entry of leukocytes and to degrade intracellular HS, an essential component for the survival of insulin-producing islet beta cells. Treatment of pre-diabetic adult NOD mice with the Hpse inhibitor PI-88 significantly reduced the incidence of T1D by ~50% and preserved islet HS. Hpse therefore acts as a novel immune effector mechanism in T1D. Our studies have identified T1D as a Hpse-dependent disease and Hpse inhibitors as novel therapeutics for preventing T1D progression and possibly the development of T1D vascular complications. PMID:24421779

  3. Chronic autoimmune thyroid disease.

    PubMed

    Litta Modignani, R; Barantani, E; Mazzolari, M; Pincetti Nervi, M; Macchi, R

    1991-01-01

    A total of 67 patients with chronic autoimmune thyroid disease were followed, mainly as outpatients, for a period of a few months to over 15 years. The diagnosis was euthyroidism (n = 16, 23.8%), subclinical hypothyroidism (n = 20, 29.8%), primary hypothyroidism (n = 28, 41.7%) or hashitoxicosis (n = 3, 4.47%). Patients with goiters fit Hashimoto's original description of "struma lymphomatosa". The diagnosis was made on clinical grounds and the usual laboratory hormonal tests. Histological examination was carried out at surgery or by fine needle aspiration in 35 patients (52.2%), and a clinical diagnosis was made in 32 (47.7%). Three patients had juvenile Hashimoto's thyroiditis. Most patients were in the fourth, fifth or sixth decade (64.8%), and of these 12 (18%) had subclinical hypothyroidism, which should be suspected when thyrotropin (TSH) is twice the upper normal limit. In these cases thyrotropin releasing hormone (TRH) testing and evaluation of anti-thyroglobulin antibodies (TgAb) and anti-microsomal antigen antibodies (MsAb) are mandatory. Hypothyroidism with few symptoms develops insidiously in young or elderly patients; the most sensitive test is TSH assay in conjunction with tests for TgAb and MsAb. L-thyroxine administration may be harmful in older patients with late diagnosed primary hypothyroidism. Thyroid supplementation is suggested for patients with subclinical hypothyroidism if TSH values are above 10 mU/L; otherwise they should be followed up annually, as should patients with positive thyroid autoantibodies who are still euthyroid. PMID:1804288

  4. Estrogens and autoimmune diseases.

    PubMed

    Cutolo, Maurizio; Capellino, Silvia; Sulli, Alberto; Serioli, Bruno; Secchi, Maria Elena; Villaggio, Barbara; Straub, Rainer H

    2006-11-01

    Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors . Several physiological, pathological, and therapeutic conditions may change the serum estrogen milieu and/or peripheral conversion rate, including the menstrual cycle, pregnancy, postpartum period, menopause, being elderly, chronic stress, altered circadian rhythms, inflammatory cytokines, and use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. In particular, cortisol and melatonin circadian rhythms are altered, at least in rheumatoid arthritis (RA), and partially involve sex hormone circadian synthesis and levels as well. Abnormal regulation of aromatase activity (i.e., increased activity) by inflammatory cytokine production (i.e., TNF-alpha, IL-1, and IL-6) may partially explain the abnormalities of peripheral estrogen synthesis in RA (i.e., increased availability of 17-beta estradiol and possible metabolites in synovial fluids) and in systemic lupus erythematosus, as well as the altered serum sex-hormone levels and ratio (i.e., decreased androgens and DHEAS). In the synovial fluids of RA patients, the increased estrogen concentration is observed in both sexes and is more specifically characterized by the hydroxylated forms, in particular 16alpha-hydroxyestrone, which is a mitogenic and cell proliferative endogenous hormone. Local effects of sex hormones in autoimmune rheumatic diseases seems to consist mainly in modulation of cell proliferation and cytokine production (i.e., TNF-alpha, Il-1, IL-12). In this respect, it is interesting that male patients with RA seem to profit more from anti-TNFalpha strategies than do female patients. PMID:17261796

  5. [Retinoid therapy for autoimmune diseases].

    PubMed

    Fukasawa, Hiroshi; Kagechika, Hiroyuki; Shudo, Koichi

    2006-06-01

    Retinoid is a collective term for compounds which bind to and activate retinoic acid receptors (RARalpha, beta, gamma and RXRalpha, beta, gamma), members of nuclear hormone receptor superfamily. The most important endogeneous retinoid is all-trans-retinoic acid (ATRA) which is an RARalpha, beta and gamma ligand. ATRA and its mimics have been in clinical use for treatment of acute promyelocytic leukemia (APL) and some skin diseases. Many synthetic retinoids have been developed and attempts to improve their medicinal properties have been made. Among them, tamibarotene (Am80) is an RARalpha- and RARbeta-specific (but RARgamma- and RXRs-nonbinding) synthetic retinoid that is effective in the treatment of psoriasis patients and relapsed APL. Experimentally, this compound is also active in animal models of rheumatoid arthritis and experimental autoimmune encephalomyelitis. On this background, possible application of retinoids for the treatment of autoimmune diseases was discussed. In particular, Th1 dominant autoimmune diseases may be the targets of the retinoids. PMID:16819260

  6. [Bullous autoimmune disorders in children].

    PubMed

    Sárdy, M; Kasperkiewicz, M

    2013-06-01

    We review the pathogenesis, clinical features, diagnosis, differential diagnosis, and therapy of autoimmune bullous skin diseases of childhood, especially of the most common linear IgA dermatosis. In autoimmune bullous diseases, autoantibodies are formed against different adhesion molecules of the skin. These are not only pathophysiologically relevant, but also serve as basis for diagnosis and follow-up of these diseases. In case an autoimmune bullous disease is suspected, histopathology and immunohistopathology (direct immunofluorescence microscopy) as well as serological tests (indirect immunofluorescence microscopy, ELISA, immunoblot) should be performed. Therapy depends on the diagnosis. In IgA-mediated pathogenesis, dapsone can be successfully used. In IgG-mediated diseases, immunosuppression with corticosteroids and steroid-sparing agents should be initiated, although only local therapy is sufficient to control a self-limiting pemphigus neonatorum. In dermatitis herpetiformis, a life-long gluten-free diet is recommended. PMID:23677541

  7. Free radical theory of autoimmunity

    PubMed Central

    Kannan, Subburaj

    2006-01-01

    Background Despite great advances in clinical oncology, the molecular mechanisms underlying the failure of chemotherapeutic intervention in treating lymphoproliferative and related disorders are not well understood. Hypothesis A hypothetical scheme to explain the damage induced by chemotherapy and associated chronic oxidative stress is proposed on the basis of published literature, experimental data and anecdotal observations. Brief accounts of multidrug resistance, lymphoid malignancy, the cellular and molecular basis of autoimmunity and chronic oxidative stress are assembled to form a basis for the hypothesis and to indicate the likelihood that it is valid in vivo. Conclusion The argument set forward in this article suggests a possible mechanism for the development of autoimmunity. According to this view, the various sorts of damage induced by chemotherapy have a role in the pattern of drug resistance, which is associated with the initiation of autoimmunity. PMID:16759382

  8. [Infectious agents and autoimmune diseases].

    PubMed

    Riebeling-Navarro, C; Madrid-Marina, V; Camarena-Medellín, B E; Peralta-Zaragoza, O; Barrera, R

    1992-01-01

    In this paper the molecular aspects of the relationships between infectious agents and autoimmune diseases, the mechanisms of immune response to infectious agents, and the more recent hypotheses regarding the cause of autoimmune diseases are discussed. The antigens are processed and selected by their immunogenicity, and presented by HLA molecules to the T cell receptor. These events initiate the immune response with the activation and proliferation of T-lymphocytes. Although there are several hypotheses regarding the cause of autoimmune diseases and too many findings against and in favor of them, there is still no conclusive data. All these hypothesis and findings are discussed in the context of the more recent advances. PMID:1615352

  9. Thyroid dysfunction: an autoimmune aspect.

    PubMed

    Khan, Farah Aziz; Al-Jameil, Noura; Khan, Mohammad Fareed; Al-Rashid, May; Tabassum, Hajera

    2015-01-01

    Auto immune thyroid disease (AITD) is the common organ specific autoimmune disorder, Hashimoto thyroiditis (HT) and Grave's disease (GD) are its well-known sequelae. It occurs due to loss of tolerance to autoantigens thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid stimulating hormone receptor (TSH-R) which leads to the infiltration of the gland. T cells in chronic autoimmune thyroiditis (cAIT) induce apoptosis in thyroid follicular cells and cause destruction of the gland. Presences of TPO antibodies are common in HT and GD, while Tg has been reported as an independent predictor of thyroid malignancy. Cytokines are small proteins play an important role in autoimmunity, by stimulating B and T cells. Various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-14, TNF-α and IFN-γ are found in thyroid follicular cells which enhance inflammatory response with nitric oxide (NO) and prostaglandins. PMID:26221205

  10. Viruses, cytokines, antigens, and autoimmunity.

    PubMed Central

    Gianani, R; Sarvetnick, N

    1996-01-01

    To explain the pathogenesis of autoimmunity, we hypothesize that following an infection the immune response spreads to tissue-specific autoantigens in genetically predisposed individuals eventually determining progression to disease. Molecular mimicry between viral and self antigens could, in some instances, initiate autoimmunity. Local elicitation of inflammatory cytokines following infection probably plays a pivotal role in determining loss of functional tolerance to self autoantigens and the destructive activation of autoreactive cells. We also describe the potential role of interleukin 10, a powerful B-cell activator, in increasing the efficiency of epitope recognition, that could well be crucial to the progression toward disease. PMID:8637859

  11. Shaking Out Clues to Autoimmune Disease

    MedlinePlus

    ... of Autoimmunity-Causing T Cells Landmark Analysis Probes Nature vs. Nurture in Multiple Sclerosis Understanding Autoimmune Diseases Immune Cells Reference: Nature. 2013 Mar 6. doi: 10.1038/nature11981. [Epub ...

  12. Cell therapy for autoimmune diseases

    PubMed Central

    Dazzi, Francesco; van Laar, Jacob M; Cope, Andrew; Tyndall, Alan

    2007-01-01

    Cell therapy, pioneered for the treatment of malignancies in the form of bone marrow transplantation, has subsequently been tested and successfully employed in autoimmune diseases. Autologous haemopoietic stem cell transplantation (HSCT) has become a curative option for conditions with very poor prognosis such as severe forms of scleroderma, multiple sclerosis, and lupus, in which targeted therapies have little or no effect. The refinement of the conditioning regimens has virtually eliminated transplant-related mortality, thus making HSCT a relatively safe choice. Although HSCT remains a nonspecific approach, the knowledge gained in this field has led to the identification of new avenues. In fact, it has become evident that the therapeutic efficacy of HSCT cannot merely be the consequence of a high-dose immuno-suppression, but rather the result of a resetting of the abnormal immune regulation underlying autoimmune conditions. The identification of professional and nonprofessional immunosuppressive cells and their biological properties is generating a huge interest for their clinical exploitation. Regulatory T cells, found abnormal in several autoimmune diseases, have been proposed as central to achieve long-term remissions. Mesenchymal stem cells of bone marrow origin have more recently been shown not only to be able to differentiate into multiple tissues, but also to exert a potent antiproliferative effect that results in the inhibition of immune responses and prolonged survival of haemopoietic stem cells. All of these potential resources clearly need to be investigated at the preclinical level but support a great deal of enthusiasm for cell therapy of autoimmune diseases. PMID:17367542

  13. Diet, microbiota and autoimmune diseases.

    PubMed

    Vieira, S M; Pagovich, O E; Kriegel, M A

    2014-05-01

    There is growing evidence that the commensal bacteria in the gastrointestinal tract (the gut microbiota) influence the development of autoimmunity in rodent models. Since humans have co-evolved with commensals for millennia, it is likely that people, who are genetically predisposed to autoimmunity, harbor gut microbial communities that similarly influence the onset and/or severity of disease. Beyond the current efforts to identify such disease-promoting or -preventing commensals ("pathobionts" or "symbionts"), it will be important to determine what factors modulate them. Dietary changes are known to affect both the composition and function of the gut microbial communities, which in turn can alter the innate and adaptive immune system. In this review, we focus on the relationships between diet, microbiota, and autoimmune diseases. We hypothesize that the beneficial and life-prolonging effects of caloric restriction on a variety of autoimmune models including lupus might partly be mediated by its effects on the gut microbiome and associated virome, the collection of all viruses in the gut. We give recent examples of the immunomodulatory potential of select gut commensals and their products or diet-derived metabolites in murine models of arthritis, multiple sclerosis, and type 1 diabetes. Lastly, we summarize the published phenotypes of germ-free mouse models of lupus and speculate on any role of the diet-sensitive microbiome and virome in systemic lupus and the related antiphospholipid syndrome. PMID:24763536

  14. Cholestatic phenotypes of autoimmune hepatitis.

    PubMed

    Czaja, Albert J

    2014-09-01

    Autoimmune hepatitis can have cholestatic features that are outside the codified diagnostic criteria. These features have uncertain effects on the clinical presentation and progression of disease. Patients with autoimmune hepatitis can have antimitochondrial antibodies and coincidental bile duct injury or loss (2%-13% of patients), focal biliary strictures and dilations based on cholangiography (2%-11%), or histologic changes of bile duct injury or loss in the absence of other features (5%-11%). These findings probably represent atypical manifestations of autoimmune hepatitis or variants of primary biliary cirrhosis or primary sclerosing cholangitis, depending on the predominant findings. Serum levels of alkaline phosphatase and γ-glutamyl transferase, histologic features of bile duct injury, and findings from cholangiography are associated with responsiveness to corticosteroid therapy and individualized alternative treatments. Corticosteroid therapy, in combination with low-dose ursodeoxycholic acid, has been promulgated by international societies, but these recommendations are not based on strong evidence. The frequency, variable outcomes, and uncertainties in diagnosis and management of the cholestatic phenotypes must be addressed by a collaborative investigational network. This network should define the genetic and pathologic features of these disorders, standardize their nomenclature, and establish a treatment algorithm. In this review, the different cholestatic phenotypes of autoimmune hepatitis, mechanisms of pathogenesis, current management strategies and outcomes, and opportunities for improving understanding and therapy are presented. PMID:24013108

  15. Rebooting autoimmunity with autologous HSCT.

    PubMed

    Snowden, John A

    2016-01-01

    Autologous hematopoietic stem cell transplantation (HSCT) is increasingly used for severe autoimmune and inflammatory diseases, but the mechanisms involved have yet to be elucidated. In this issue of Blood, Delemarre et al report their findings in both animal and human models which provide insights into restoration of functionality and diversity within the regulatory T-cell (Treg) compartment following HSCT. PMID:26744435

  16. Rethinking Mechanisms of Autoimmune Pathogenesis

    PubMed Central

    Pillai, Shiv

    2016-01-01

    Why exactly some individuals develop autoimmune disorders remains unclear. The broadly accepted paradigm is that genetic susceptibility results in some break in immunological tolerance, may enhance the availability of autoantigens, and may enhance inflammatory responses. Some environmental insults that occur on this background of susceptibility may then contribute to autoimmunity. In this review we discuss some aspects related to inhibitory signaling and rare genetic variants, as well as additional factors that might contribute to autoimmunity including the possible role of clonal somatic mutations, the role of epigenetic events and the contribution of the intestinal microbiome. Genetic susceptibility alleles generally contribute to the loss of immunological tolerance, the increased availability of asutoantigens, or an increase in inflammation. Apart from common genetic variants, rare loss-of-function genetic variants may also contribute to the pathogenesis of autoimmunity. Studies of an inhibitory signaling pathway in B cells helped identify a negative regulatory enzyme called sialic acid acetyl esterase. The study of rare genetic variants of this enzyme provides an illustrative example showing the importance of detailed functional analyses of variant alleles and the need to exclude functionally normal common or rare genetic variants from analysis. It has also become clear that pathways that are functionally impacted by either common or rare defective variants can also be more significantly compromised by gene expression changes that may result from epigenetic alterations. Another important and evolving area that has been discussed relates to the role of the intestinal microbiome in influencing helper T cell polarization and the development of autoimmunity. PMID:23809879

  17. Thyroid autoimmunity in pregnant Nigerians

    PubMed Central

    Kayode, Oluwatosin O.; Odeniyi, Ifedayo A.; Iwuala, Sandra; Olopade, Oluwarotimi B.; Fasanmade, Olufemi A.; Ohwovoriole, Augustine E.

    2015-01-01

    Context: Thyroid autoimmunity is a recognized disorder in pregnancy and is associated with a number of adverse pregnancy outcomes. Aim: This study set out to determine the relationship between pregnancy and thyroid autoimmunity in Nigerian women. Settings and Design: This was an analytical cross-sectional study carried out in a tertiary hospital in South Western Nigeria with a total study population of 108 pregnant and 52 nonpregnant women. Subjects and Methods: Serum thyroid stimulating hormone, free thyroxine and thyroid peroxidase antibodies (TPO-Ab) were quantitatively determined using enzyme linked immuno-assays. Pregnant women were grouped into three categories (<14 weeks, 14–28 weeks and > 28 weeks). The relationship between pregnancy and thyroid autoimmunity was determined using Spearman correlation. Analysis of variance was used in comparison of means, Chi-square test used in analyzing proportions while P ≤ 0.05 was considered as significant. Results: The mean age of the pregnant women was 30.4 ± 6.0 years while the mean gestational age of all pregnant women was 20.6 ± 9.6 weeks. The mean TPO-Ab of 11.58 IU/ml in the pregnant was significantly higher than that of the controls of 7.23 IU/ml (P < 0.001). Out of 108 pregnant women, 27 (25%) had elevated TPO-Ab as against about 2% of the nonpregnant women levels P < 0.001. The number of pregnant women with elevated TPO-Ab levels decreased from 33.3% in the first group to 25.6% and 15.2% in the second and third groups. Conclusion: Thyroid autoimmunity expressed by the presence of TPO-Ab is high among pregnant Nigerian women and the frequency of autoimmunity appears to decline with advancing gestational age. PMID:26425470

  18. Gravi-sensing microorganisms as model systems for gravity sensing in eukaryotes

    NASA Astrophysics Data System (ADS)

    Streb, C.; Richter, P.; Lebert, M.; Häder, D.-P.

    2001-08-01

    Gravi-sensing in single cells and multicellular organisms is a very active field of investigation. Similarities between gravity sensing mechanisms in uni- and multicellular eukaryotes make single cells ideal model systems for the understanding of gravity responses on the cellular and molecular level with far fetching significance for other systems. This article gives a short overview about gravi-sensing in plants (Arabidopsis, Chara) as well as the ciliates Loxodes and Paramecium and concentrates on gravitaxis research in the single cellular flagellate, Euglena gracilis. Experiments revealed the involvement of cAMP, Ca2+ specific mechanosensitive channels and membrane potential in the signal transduction chain of gravitaxis. Future perspectives for the use of motile, photosynthetic and other unicellular microorganisms for space applications e.g. for oxygen supply in life support systems or research on the origin of life are discussed.

  19. MicroRNA in autoimmunity and autoimmune diseases

    PubMed Central

    Pauley, Kaleb M.; Cha, Seunghee; Chan, Edward K.L.

    2009-01-01

    MicroRNAs (miRNAs) are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3′ untranslated region (UTR) of specific messenger RNAs (mRNAs) for degradation or translational repression. miRNA-mediated gene regulation is critical for normal cellular functions such as the cell cycle, differentiation, and apoptosis, and as much as one-third of human mRNAs may be miRNA targets. Emerging evidence has demonstrated that miRNAs play a vital role in the regulation of immunological functions and the prevention of autoimmunity. Here we review the many newly discovered roles of miRNA regulation in immune functions and in the development of autoimmunity and autoimmune disease. Specifically, we discuss the involvement of miRNA regulation in innate and adaptive immune responses, immune cell development, T regulatory cell stability and function, and differential miRNA expression in rheumatoid arthritis and systemic lupus erythematosus. PMID:19303254

  20. Animal Models of Autoimmune Neuropathy

    PubMed Central

    Soliven, Betty

    2014-01-01

    The peripheral nervous system (PNS) comprises the cranial nerves, the spinal nerves with their roots and rami, dorsal root ganglia neurons, the peripheral nerves, and peripheral components of the autonomic nervous system. Cell-mediated or antibody-mediated immune attack on the PNS results in distinct clinical syndromes, which are classified based on the tempo of illness, PNS component(s) involved, and the culprit antigen(s) identified. Insights into the pathogenesis of autoimmune neuropathy have been provided by ex vivo immunologic studies, biopsy materials, electrophysiologic studies, and experimental models. This review article summarizes earlier seminal observations and highlights the recent progress in our understanding of immunopathogenesis of autoimmune neuropathies based on data from animal models. PMID:24615441

  1. Propylthiouracil-induced autoimmune disease

    PubMed Central

    Paiaulla, Santosh; Venkategowda, Pradeep Marur; Rao, S. Manimala; Balaraju, Banda

    2015-01-01

    Hyperthyroidism is a condition characterized by excessive production of thyroid hormones. Propylthiouracil (PTU) is commonly used as first line drug in the management of hyperthyroidism. This is a case report of 24-year-old female, a known case of hyperthyroidism since 4 years, who came with a history of fever and myalgia since 3 days and dyspnea with coughing out of blood since 1 day. Patient was taking PTU (100 mg per day) since 4 years for hyperthyroidism. Patient was immediately intubated for type-II respiratory failure. Diagnosed to be having PTU-induced autoimmune disease. PTU was stopped and treated with methylprednisolone and cyclophosphamide. Clinical features improved over a period of 8 days and discharged home successfully. Having a high suspicion for the onset of autoimmune disease in hyperthyroidism patients who are on PTU therapy and timely treatment with immunosuppressants and supportive care along with the withdrawal of the drug can make a difference in morbidity and mortality. PMID:26321810

  2. Progranulin antibodies in autoimmune diseases.

    PubMed

    Thurner, Lorenz; Preuss, Klaus-Dieter; Fadle, Natalie; Regitz, Evi; Klemm, Philipp; Zaks, Marina; Kemele, Maria; Hasenfus, Andrea; Csernok, Elena; Gross, Wolfgang L; Pasquali, Jean-Louis; Martin, Thierry; Bohle, Rainer Maria; Pfreundschuh, Michael

    2013-05-01

    Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. PMID:23149338

  3. [Autoimmune hepatitis induced by isotretionine].

    PubMed

    Guzman Rojas, Patricia; Gallegos Lopez, Roxana; Ciliotta Chehade, Alessandra; Scavino, Yolanda; Morales, Alejandro; Tagle, Martín

    2016-01-01

    We describe a case of a teenage patient with the diagnosis of drug induced autoimmune hepatitis. The patient is a 16 years old female, with the past medical history of Hashimoto’s hypothyroidism controlled with levothyroxine, who started treatment with Isotretionin (®Accutane) 20 mg q/12 hours for a total of 3 months for the treatment of severe acne. The physical examination was within normal limits and the results of the laboratory exams are: Baseline values of ALT 28 U/L, AST 28 U/L. Three months later: AST 756 U/L, ALT 1199U/L, alkaline phosphatase 114 U/L, with normal bilirrubin levels throughout the process. The serology studies were negative for all viral hepatitis; ANA titers were positive (1/160) and igG levels were also elevated. A liver biopsy was performed, and was compatible with the diagnosis of autoimmune hepatitis. Corticosteroid therapy was started with Prednisone 40 mg per day one week after stopping the treatment with isotretionin, observing an improvement in the laboratory values. We describe this case and review the world literature since there are no reported cases of Isotretinoin-induced autoimmune hepatitis. PMID:27131947

  4. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    PubMed Central

    Saif, Muhammad Wasif

    2014-01-01

    Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis. PMID:24839445

  5. Autoimmunity in primary T-cell immunodeficiencies.

    PubMed

    Azizi, Gholamreza; Ghanavatinejad, Alireza; Abolhassani, Hassan; Yazdani, Reza; Rezaei, Nima; Mirshafiey, Abbas; Aghamohammadi, Asghar

    2016-09-01

    Primary immunodeficiency diseases (PID) are a genetically heterogeneous group of more than 270 disorders that affect distinct components of both humoral and cellular arms of the immune system. Primary T cell immunodeficiencies affect subjects at the early age of life. In most cases, T-cell PIDs become apparent as combined T- and B-cell deficiencies. Patients with T-cell PID are prone to life-threatening infections. On the other hand, non-infectious complications such as lymphoproliferative diseases, cancers and autoimmunity seem to be associated with the primary T-cell immunodeficiencies. Autoimmune disorders of all kinds (organ specific or systemic ones) could be subjected to this class of PIDs; however, the most frequent autoimmune disorders are immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). In this review, we discuss the proposed mechanisms of autoimmunity and review the literature reported on autoimmune disorder in each type of primary T-cell immunodeficiencies. PMID:27063703

  6. Autoimmune thrombocytopenia (AITP) and thyroid autoimmune disease (TAD): overlapping syndromes?

    PubMed Central

    Cordiano, I; Betterle, C; Spadaccino, C A; Soini, B; Girolami, A; Fabris, F

    1998-01-01

    The pathogenesis of thrombocytopenia associated with TAD and the occurrence of overlapping traits between TAD and AITP are still a matter of debate. For this reason, we investigated for the presence and specificity of platelet and thyroid autoantibodies in 18 TAD patients with thrombocytopenia, 19 TAD patients without thrombocytopenia and in 22 patients with primary AITP without clinical signs of TAD. Platelet-associated IgG and/or specific circulating platelet autoantibodies were detected in 83% of patients with TAD and thrombocytopenia, in 10% of patients with TAD without thrombocytopenia and in 86% of patients with primary AITP. The reactivity of serum autoantibodies, assayed by MoAb immobilization of platelet antigens (MAIPA), was directed against platelet glycoproteins Ib and/or IIb/IIIa in 50% of the patients with TAD and thrombocytopenia, as in 46% of the patients with primary AITP. Thyroid autoantibodies were found in 89% of patients with TAD and thrombocytopenia, in 95% of patients with TAD without thrombocytopenia, and in 18% of patients with primary AITP. Thyrotropin (TSH) levels determined in three of four AITP patients with thyroid autoantibodies revealed a subclinical hyperthyroidism in one patient. The present study supports the autoimmune aetiology of thrombocytopenia associated with TAD, since the prevalence and specificity of platelet autoantibodies are similar in TAD and primary AITP. The results indicate also that there exists an overlap between thyroid and platelet autoimmunity with or without clinical manifestations. PMID:9737665

  7. Anatabine ameliorates experimental autoimmune thyroiditis.

    PubMed

    Caturegli, Patrizio; De Remigis, Alessandra; Ferlito, Marcella; Landek-Salgado, Melissa A; Iwama, Shintaro; Tzou, Shey-Cherng; Ladenson, Paul W

    2012-09-01

    Tobacco smoking favorably influences the course of Hashimoto thyroiditis, possibly through the antiinflammatory proprieties of nicotine. In this study we tested anatabine, another tobacco alkaloid, in a model of experimental autoimmune thyroiditis. Experimental autoimmune thyroiditis was induced by different doses of thyroglobulin, to produce a disease of low, moderate, or high severity, in 88 CBA/J female mice: 43 drank anatabine supplemented water and 45 regular water. Mice were bled after immunization and killed to assess thyroid histopathology, thyroglobulin antibodies, T(4), and thyroid RNA expression of 84 inflammatory genes. We also stimulated in vitro a macrophage cell line with interferon-γ or lipopolysaccharide plus or minus anatabine to quantitate inducible nitric oxide synthase and cyclooxygenase 2 protein expression. Anatabine reduced the incidence and severity of thyroiditis in the moderate disease category: only 13 of 21 mice (62%) developed thyroid infiltrates when drinking anatabine as compared with 22 of 23 (96%) controls (relative risk 0.59, P = 0.0174). The median thyroiditis severity was 0.5 and 2.0 in anatabine and controls, respectively (P = 0.0007 by Wilcoxon rank sum test). Anatabine also reduced the antibody response to thyroglobulin on d 14 (P = 0.029) and d 21 (P = 0.045) after immunization and improved the recovery of thyroid function on d 21 (P = 0.049). In the thyroid transcriptome, anatabine restored expression of IL-18 and IL-1 receptor type 2 to preimmunization levels. Finally, anatabine suppressed in a dose-dependent manner macrophage production of inducible nitric oxide synthase and cyclooxygenase 2. Anatabine ameliorates disease in a model of autoimmune thyroiditis, making the delineation of its mechanisms of action and potential clinical utility worthwhile. PMID:22807490

  8. Genetics Home Reference: congenital myasthenic syndrome

    MedlinePlus

    ... Advocacy Resources (2 links) Muscular Dystrophy Association Myasthenia Gravis Foundation of America: Congenital Myasthenia GeneReviews (1 link) ... for professional medical care or advice. Users with questions about a personal health condition should consult with ...

  9. Electromyography

    MedlinePlus

    ... by a number of disorders, including muscular dystrophy ) Myasthenia gravis Peripheral neuropathy Polymyositis Radial nerve dysfunction Sciatic ... Mononeuritis multiplex Mononeuropathy Multiple system atrophy Muscular dystrophy Myasthenia ... neuropathy Polymyositis - adult Radial nerve dysfunction ...

  10. Thymoma with Autoimmune Hemolytic Anemia

    PubMed Central

    Suzuki, Kensuke; Inomata, Minehiko; Shiraishi, Shiori; Hayashi, Ryuji; Tobe, Kazuyuki

    2014-01-01

    A 38-year-old Japanese male was referred to our hospital with abnormal chest X-ray results and severe Coombs-positive hemolytic anemia. He was diagnosed with a stage IV, WHO type A thymoma and was treated with oral prednisolone (1 mg/kg/day) and subsequent chemotherapy. After chemotherapy, the patient underwent surgical resection of the thymoma. Hemolysis rapidly disappeared and did not return after the discontinuation of oral corticosteroids. Corticosteroid therapy may be preferable to chemotherapy or thymoma surgical resection in the management of autoimmune hemolytic anemia with thymoma. PMID:25722666

  11. The Immunogenetics of Autoimmune Cholestasis.

    PubMed

    Trivedi, Palak J; Hirschfield, Gideon M

    2016-02-01

    The immune-mediated hepatobiliary diseases, primary biliary cirrhosis and primary sclerosing cholangitis are relatively rare, albeit and account for a significant amount of liver transplant activity and liver-related mortality globally. Precise disease mechanisms are yet to be described although a contributory role of genetic predisposition is firmly established. In addition to links with the major histocompatibility complex, a number of associations outside this region harbor additional loci which underscore the fundamental role of breaks in immune tolerance and mucosal immunogenicity in the pathogenesis of autoimmune biliary disease. We provide an overview of these key discoveries before discussing putative avenues of therapeutic exploitation based on existing findings. PMID:26593288

  12. Therapy of autoimmune bullous diseases

    PubMed Central

    Mutasim, Diya F

    2007-01-01

    Autoimmune bullous diseases result from an immune response to molecular components of the desmosome or basement membrane. Bullous diseases are associated with a high degree of morbidity and occasional mortality. Therapy of bullous diseases consists of suppressing the immune system, controlling inflammation and improving healing of erosions. The therapeutic agents used in the treatment of bullous diseases may be associated with high morbidity and occasional mortality. Successful treatment requires understanding of the pathophysiology of the disease process and the pharmacology of the drugs being used. PMID:18360613

  13. Autoimmune Cytopenias In Common Variable Immunodeficiency

    PubMed Central

    Podjasek, Jenna C.; Abraham, Roshini S.

    2012-01-01

    Common variable immunodeficiency (CVID) is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20–50%; Chapel et al., 2008; Cunningham-Rundles, 2008), autoimmune cytopenias are by far the most common occurring variably in 4–20% (Michel et al., 2004; Chapel et al., 2008) of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia, and neutropenia. While it may seem paradoxical “prima facie” that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21 low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID. PMID:22837758

  14. Autoimmune cytopenias in common variable immunodeficiency.

    PubMed

    Podjasek, Jenna C; Abraham, Roshini S

    2012-01-01

    Common variable immunodeficiency (CVID) is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20-50%; Chapel et al., 2008; Cunningham-Rundles, 2008), autoimmune cytopenias are by far the most common occurring variably in 4-20% (Michel et al., 2004; Chapel et al., 2008) of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia, and neutropenia. While it may seem paradoxical "prima facie" that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21 low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID. PMID:22837758

  15. Effects of nisin and temperature on survival, growth, and enterotoxin production characteristics of psychrotrophic Bacillus cereus in beef gravy.

    PubMed

    Beuchat, L R; Clavero, M R; Jaquette, C B

    1997-05-01

    The presence of psychrotrophic enterotoxigenic Bacillus cereus in ready-to-serve meats and meat products that have not been subjected to sterilization treatment is a public health concern. A study was undertaken to determine the survival, growth, and diarrheal enterotoxin production characteristics of four strains of psychrotrophic B. cereus in brain heart infusion (BHI) broth and beef gravy as affected by temperature and supplementation with nisin. A portion of unheated vegetative cells from 24-h BHI broth cultures was sensitive to nisin as evidenced by an inability to form colonies on BHI agar containing 10 micrograms of nisin/ml. Heat-stressed cells exhibited increased sensitivity to nisin. At concentrations as low as 1 microgram/ml, nisin was lethal to B. cereus, the effect being more pronounced in BHI broth than in beef gravy. The inhibitory effect of nisin (1 microgram/ml) was greater on vegetative cells than on spores inoculated into beef gravy and was more pronounced at 8 degrees C than at 15 degrees C. Nisin, at a concentration of 5 or 50 micrograms/ml, inhibited growth in gravy inoculated with vegetative cells and stored at 8 or 15 degrees C, respectively, for 14 days. Growth of vegetative cells and spores of B. cereus after an initial period of inhibition is attributed to loss of activity of nisin. One of two test strains produced diarrheal enterotoxin in gravy stored at 8 or 15 degrees C within 9 or 3 days, respectively. Enterotoxin production was inhibited in gravy supplemented with 1 microgram of nisin/ml and stored at 8 degrees C for 14 days; 5 micrograms of nisin/ml was required for inhibition at 15 degrees C. Enterotoxin was not detected in gravy in which less than 5.85 log10 CFU of B. cereus/ml had grown. Results indicate that as little as 1 microgram of nisin/ml may be effective in inhibiting or retarding growth of and diarrheal enterotoxin production by vegetative cells and spores of psychrotrophic B. cereus in beef gravy at 8 degrees C, a

  16. Cystic Lesions in Autoimmune Pancreatitis.

    PubMed

    Gompertz, Macarena; Morales, Claudia; Aldana, Hernán; Castillo, Jaime; Berger, Zoltán

    2015-01-01

    Autoimmune pancreatitis (AIP) can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases. PMID:26675058

  17. Cardiovascular Involvement in Autoimmune Diseases

    PubMed Central

    Amaya-Amaya, Jenny

    2014-01-01

    Autoimmune diseases (AD) represent a broad spectrum of chronic conditions that may afflict specific target organs or multiple systems with a significant burden on quality of life. These conditions have common mechanisms including genetic and epigenetics factors, gender disparity, environmental triggers, pathophysiological abnormalities, and certain subphenotypes. Atherosclerosis (AT) was once considered to be a degenerative disease that was an inevitable consequence of aging. However, research in the last three decades has shown that AT is not degenerative or inevitable. It is an autoimmune-inflammatory disease associated with infectious and inflammatory factors characterized by lipoprotein metabolism alteration that leads to immune system activation with the consequent proliferation of smooth muscle cells, narrowing arteries, and atheroma formation. Both humoral and cellular immune mechanisms have been proposed to participate in the onset and progression of AT. Several risk factors, known as classic risk factors, have been described. Interestingly, the excessive cardiovascular events observed in patients with ADs are not fully explained by these factors. Several novel risk factors contribute to the development of premature vascular damage. In this review, we discuss our current understanding of how traditional and nontraditional risk factors contribute to pathogenesis of CVD in AD. PMID:25177690

  18. Susceptibility Genes in Thyroid Autoimmunity

    PubMed Central

    Ban, Yoshiyuki; Tomer, Yaron

    2005-01-01

    The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine) is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT) and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg). Most likely, these loci interact and their interactions may influence disease phenotype and severity. PMID:15712599

  19. Weakness

    MedlinePlus

    ... spine) Stroke MUSCLE DISEASES Becker muscular dystrophy Dermatomyositis Muscular dystrophy (Duchenne) Myotonic dystrophy POISONING Botulism Poisoning ( insecticides , nerve gas) Shellfish poisoning OTHER Anemia Myasthenia gravis Polio

  20. Defining and analyzing geoepidemiology and human autoimmunity.

    PubMed

    Shapira, Yinon; Agmon-Levin, Nancy; Shoenfeld, Yehuda

    2010-05-01

    Autoimmune diseases cumulatively affect 5-10% of the industrial world population and are a significant cause of morbidity and mortality. In recent decades rates are rising worldwide, and autoimmunity can no longer be associated solely with the more developed "Western" countries. Geoepidemiology of autoimmune diseases portrays the burden of these illnesses across various regions and ethnic populations. Furthermore, Geoepidemiology may yield important clues to the genetic and triggering environmental mechanisms of autoimmunity. In this review we compiled and discuss in depth abundant geoepidemiological data pertaining to four major autoimmune conditions, namely type-1 diabetes mellitus, multiple sclerosis, autoimmune thyroid disease, and inflammatory bowel disease. The following key results manifested in this review: 1) Ethno-geographic gradients in autoimmune disease risk are attributable to a complex interplay of genetic and environmental pressures. 2) Industrial regions, particularly Northern Europe and North America, still exhibit the highest rates for most autoimmune diseases. 3) Methods particularly useful in demonstrating the significant influence of genetic and environmental factors include comparative ethnic differences studies, migration studies, and recognition of 'hotspots'. 4) Key environmental determinants of geographical differences include diminished ultraviolet radiation exposure, Western or affluence-related lifestyle, infection exposure, environmental pollutants, nutritional factors and disease-specific precipitants (e.g., iodine exposure). PMID:20034761