Passive transfer models of myasthenia gravis with muscle-specific kinase antibodies

Passive transfer of experimental autoimmune myasthenia gravis (EAMG) was achieved using the gamma globulin fraction and purified IgG from sera of rats immunized with Electrophus electricus (eel) acetylcholine receptor (AChR). This demonstrates the critical role of anti-AChR antibodies in impairing neuromuscular transmission in EAMG. Passive transfer of anti-AChR antibodies from rats with chronic EAMG induced signs of the acute phase of EAMG in normal recipient rats, including invasion of the motor end-plate region by mononuclear inflammatory cells. Clinical, eletrophysiological, histological, and biochemical signs of acute EAMG were observed by 24 h after antibody transfer. Recipient rats developed profound weakness and fatigability, and the posture characteristic of EAMG. Striking weight loss was attributable to dehydration. Recipient rats showed large decreases in amplitude of muscle responses to motor nerve stimulation, and repetitive nerve stimulation induced characteristic decrementing responses. End-plate potentials were not detectable in many muscle fibers, and the amplitudes of miniature end-plate potentials were reduced in the others. Passively transferred EAMG more severely affected the forearm muscles than diaphragm muscles, though neuromuscular transmission was impaired and curare sensitivity was increased in both muscles. Some AChR extracted from the muscles of rats with passively transferred EAMG was found to be complexed with antibody, and the total yield of AChR per rat was decreased. The quantitative decrease in AChR approximately paralleled in time the course of clinical and electrophysiological signs. The amount of AChR increased to normal levels and beyond at the time neuromuscular transmission was improving. The excess of AChR extractable from muscle as the serum antibody level decreased probably represented extrajunctional receptors formed in response to functional denervation caused by phagocytosis of the postsynaptic membrane by macrophages. The amount of antibody required to passively transfer EAMG was less than required to bind all AChR molecules in a rat's musculature. The effectiveness of samll amounts of antibody was probably amplified by the activation of complement and by the destruction of large areas of postsynaptic membrane by phagocytic cells. A self-sustaining autoimmune response to AChR was not provoked in animals with passively transferred EAMG.

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Muscle-specific kinase antibody associated myasthenia gravis after bone marrow transplantation

Neuromuscular Disorders ◽

10.1016/j.nmd.2013.11.005 ◽

2014 ◽

Vol 24 (2) ◽

pp. 148-150 ◽

Cited By ~ 6

Author(s):

Zeinab Heidarzadeh ◽

Seyyed-Asadollah Mousavi ◽

Vahid Reza Ostovan ◽

Shahriar Nafissi

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Myasthenia Gravis ◽

Marrow Transplantation ◽

Muscle Specific Kinase

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Clinical Profile of Patients with Myasthenia Gravis in a Tertiary Center of Nepal

Nepal Journal of Neuroscience ◽

10.3126/njn.v14i1.20659 ◽

2017 ◽

Vol 14 (1) ◽

pp. 14-17

Author(s):

Rajeev Ojha ◽

Krishna K Oli ◽

Bikram P Gajurel ◽

Ragesh Karn ◽

Reema Rajbhandari ◽

...

Keyword(s):

Myasthenia Gravis ◽

Age Of Onset ◽

High Sensitivity ◽

Diagnostic Methods ◽

University Teaching ◽

Outpatient Department ◽

Repetitive Nerve Stimulation ◽

Tertiary Center ◽

Muscle Specific Kinase ◽

Antibody Tests

Myasthenia gravis (MG) has a cosmopolitan distribution and can affect people of all age group. Sometimes atypical presentation causes difficulty in the early diagnosis and management. Our aim is to study the clinical subtypes and manifestations of MG along with serological and electrophysiological diagnostic methods. Patients who were admitted in Neurology department or presented in Neurology outpatient department of Tribhuvan University Teaching Hospital from 2015 March to 2016 November were retrospectively reviewed. Out of 28 patients reviewed, 23 patients were included in the study. Their mean age of onset was 40.4±19.2 years; range=12 – 78 years, and 12 of them were female (52.2%). Eight patients (34.8%) were diagnosed with ocular myasthenia and 15 were patients (65.2%) of General Myasthenia. Seventeen patients (73.9%) were acetylcholine receptor (AChR) antibodies positive, one female patient was found to be muscle specific kinase (MuSK) positive. Decremental pattern in Repetitive Nerve stimulation (RNS) was reported in 11 patients (47.8%) and ice pack test was positive in 16 patients (69.3%). Ophthalmological findings are the most common presentation of MG patients. Icepack test is an easy clinical diagnostic tool for outpatient department which has both high sensitivity and specificity. RNS and antibody tests are the supporting tests useful for confirming the diagnosis.Nepal Journal of Neuroscience, Volume 14, Number 1, 2017, Page: 14-17

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Dysautonomia as the Presenting Symptom in Anti-Muscle-Specific Kinase Antibody Myasthenia Gravis

Journal of Neuromuscular Diseases ◽

10.3233/jnd-190411 ◽

2020 ◽

Vol 7 (1) ◽

pp. 47-50

Author(s):

T.J.S. Bekooij ◽

H.J. Gilhuis ◽

L. Dawson ◽

E.H. Niks

Keyword(s):

Myasthenia Gravis ◽

Muscle Specific Kinase

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Plasma vitronectin is reduced in patients with myasthenia gravis: Diagnostic and pathophysiological potential

Journal of Circulating Biomarkers ◽

10.1177/1849454419875912 ◽

2019 ◽

Vol 8 ◽

pp. 184945441987591 ◽

Cited By ~ 3

Author(s):

Antonio Junior Lepedda ◽

Giovanni Andrea Deiana ◽

Omar Lobina ◽

Gabriele Nieddu ◽

Paola Baldinu ◽

...

Keyword(s):

Immune Response ◽

Extracellular Matrix ◽

Myasthenia Gravis ◽

Cell Attachment ◽

Postsynaptic Membrane ◽

Clinical Value ◽

Disease Biomarkers ◽

Skeletal Muscle Weakness ◽

Plasma Fractions ◽

Muscle Specific Kinase

Myasthenia gravis (MG) is an autoimmune disease leading to varying degrees of skeletal muscle weakness. It is caused by specific antibodies directed against definite components in the postsynaptic membrane at the neuromuscular junction (NMJ), such as the acetylcholine receptor (AChR) and the muscle-specific kinase (MUSK) receptor. In clinical practice, MG patients may be classified into three main subgroups based on the occurrence of serum autoantibodies directed against AChR or MUSK receptor or antibody-negative. As the MG subgroups differ in terms of clinical characteristics, disease pathogenesis, prognosis, and response to therapies, they could benefit from targeted treatment as well as the detection of other possible disease biomarkers. We performed proteomics on plasma fractions enriched in low-abundance proteins to identify potential biomarkers according to different autoimmune responses. By this approach, we evidenced a significant reduction of vitronectin in MG patients compared to healthy controls, irrespective of the autoantibodies NMJ target. The obtained results were validated by mono- and two-dimensional Western blotting analysis. Vitronectin is a multifunctional glycoprotein involved in the regulation of several pathophysiological processes, including complement-dependent immune response, coagulation, fibrinolysis, pericellular proteolysis, cell attachment, and spreading. The pathophysiological significance of the reduction of plasma vitronectin in MG patients has yet to be fully elucidated. It could be related either to a possible deposition of vitronectin at NMJ to counteract the complement-mediated muscle damage at this level or to a parallel variation of this glycoprotein in the muscle extracellular matrix with secondary induced alteration in clustering of AChRs at NMJ, as it occurs with variation in concentrations of agrin, another extracellular matrix component. The clinical value of measuring plasma vitronectin has yet to be defined. According to present findings, significantly lower plasma values of this glycoprotein might be indicative of an impaired complement-dependent immune response.

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