scholarly journals Polymorphism of clinical phenotypes and heterogeneity of autoimmune targets of myasthenia gravis

2020 ◽  
Keyword(s):  
Myasthenia Gravis ◽  
Mitotic Cell ◽  
Clinical Phenotypes ◽  
Autoimmune Antibodies ◽  
Thymus Hyperplasia ◽  
Nuclear Antigens ◽  
Antinuclear Autoantibodies ◽  
Maximum Titer ◽  
Centromeric Protein ◽  
Nuclear Structures

Abstract. The aim of the study was to evaluate the presence of autoantibodies to different subunits of nAChR and nuclear antigens at different myasthenia phenotypes. The work has investigated the presence of antibodies to α1- and α7-subunits of nAChR, the repertoire and frequency of occurrence of antinuclear autoantibodies in different clinical phenotypes of myasthenia to understand the mechanisms of pathogenesis of various forms of the disease. Additional factors of autoimmunization were identified that affect certain mechanisms of pathogenesis in thymus-independent and thymus-dependent myasthenia gravis. Autoantibodies to α1 and α7 subunits of nAChR were detected in case of thymus-independent myasthenia gravis and thymus-dependent myasthenia gravis with thymus hyperplasia or locally spread thymoma, as well as the presence of antinuclear antibodies in case of thymoma on the background of myasthenia gravis. Autoantibodies to the α1 subunit of nAChR are available in all patients with thymus-independent and thymus-dependent myasthenia gravis; the maximum titer was in patients with myasthenia and thymus hyperplasia. The presence of autoimmune antibodies to another target – to the α7 subunit of nAChR was found in patients with thymus-independent myasthenia gravis and with myasthenia and thymus hyperplasia. Detected anti-nuclear antibodies (ANA) in patients with thymoma, are preferably antibodies to structures that are directly involved in mitotic cell division, that is to centromere, to centromeric protein F, to the centrosomal protein of achromatin spindle – NuMa and MSA-2 antigen mitotic spindle that affects the course of cell proliferation, reparative and regenerative processes in tissues. The selectivity of antibody damage by the subunit of NAHR in different myasthenia phenotypes and the presence of ANA in thymus-dependent myasthenia with thymoma has great diagnostic and prognostic value. The presence of specific autoantibodies to certain nuclear structures of the cell, along with other autoimmunization mechanisms, affects various metabolic mechanisms and can be used to select targeted therapy taking into account individual pathogenic targets of the autoimmune process.

scholarly journals Features of self-tolerance loss in patients with different clinical phenotypes of myasthenia

2018 ◽  
Vol 9 (4) ◽  
pp. 561-567
Author(s):  
E. M. Klimova ◽  
D. V. Minuchin ◽  
L. A. Drozdova ◽  
E. V. Lavinskaya ◽  
T. I. Kordon ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Treatment Protocol ◽  
Immunoglobulin Therapy ◽  
Autoimmune Reaction ◽  
Clinical Phenotypes ◽  
Reactive Protein ◽  
Thymus Hyperplasia ◽  
Self Tolerance ◽  
Group A ◽  
Treg Lymphocytes

The incidence of myasthenia gravis which is characterized by progressive muscular weakness on the background of structural disorders of the thymus, has increased. Myasthenia gravis is a multifactorial autoimmune disease, it has a pronounced clinical heterogeneity, and therefore the standard diagnostic and treatment protocol is not always effective. To substantiate an individual approach to the treatment of various clinical forms of myasthenia, we conducted a study of mechanisms and markers of loss of central and peripheral self-tolerance in thymus-independent myasthenia (M) and thymus-dependent myasthenia gravis with thymus hyperplasia (MH) and thymoma (MT), involving a total of 427 patients examined. In patients with different phenotypes of myasthenia, we used the methods of spectrophotometry, flow cytometry, enzyme immunoassay. In patients with MH on the background of lymphofollicular thymus hyperplasia we revealed a pronounced humoral sensitization in comparison with the reference values: the concentration of C4 complement, C-reactive protein, circulating immune complexes and the initiation of an indirect autoimmune reaction a reliable increase in autoantibodies (AAbs) to the α1 and α7 subunit of subunit of nicotinic receptors (nAChR). In M and MT groups a high similar titer of AAbs to other epitopes was revealed: DNA, β2-glycoprotein I, membranes of intestinal and stomach cells, lung, liver, kidney cells. A pronounced blast-transforming response to the presence of the mitogen PHA was revealed in the MT group. In the MT group, a decrease in the content of CD4+ CD28+ co-stimulatory molecules and in the MH group, a decrease in СD4+ CD25+ Treg lymphocytes was revealed. Individual methods for correcting the loss of self-tolerance in patients with different clinical phenotypes of myasthenia were justified taking into account the use of immunosuppression, specific viral-neutralizing immunoglobulins and massive IgG immunoglobulin therapy, and the application of anti-inflammatory recombinant interleukins.

scholarly journals Pleiotropic effects of the 8.1 HLA haplotype in patients with autoimmune myasthenia gravis and thymus hyperplasia

2004 ◽  
Vol 101 (43) ◽  
pp. 15464-15469 ◽  
Author(s):  
C. Vandiedonck ◽  
G. Beaurain ◽  
M. Giraud ◽  
C. Hue-Beauvais ◽  
B. Eymard ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Pleiotropic Effects ◽  
Thymus Hyperplasia ◽  
Autoimmune Myasthenia

scholarly journals Impact of Different Thymic Pathologies on the Clinical Course of Myasthenia Gravis: A Population Wide Study in Latvia / Aizkrūts Dziedzera Patoloģiju Ietekmeu uz Myasthenia Gravis Klīnisko Gaitu: Populācijas Pētījums Latvijā

2015 ◽  
Vol 69 (5) ◽  
pp. 210-214
Author(s):  
Anete Zieda ◽  
Kristīne Rāviņa ◽  
Lelde Pelčere ◽  
Maruta S. Naudiņa ◽  
Inese Kamša ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Symptom Severity ◽  
Neuromuscular Transmission ◽  
Clinical Course ◽  
Published Data ◽  
Test Results ◽  
Thymus Hyperplasia ◽  
Electrophysiological Test ◽  
Potential Impact ◽  
Almost All

Abstract Myasthenia gravis (MG) is an autoimmune disease characterized by autoantibody mediated postsynaptic failure of neuromuscular transmission. The thymus gland has a role in the pathogenesis of MG. The aim of this study was to determine (1) the prevalence of different thymic pathologies in the MG patient population of Latvia; (2) the potential impact of different thymus pathologies on the clinical course of MG; and (3) the effectiveness of surgical treatment of thymic pathologies in Latvia. The results showed that the most common thymus pathology among the patients with MG in Latvia is thymoma. Compared to the published data, the proportion of MG patients diagnosed with thymus hyperplasia in Latvia is very small. Thymus hyperplasia is uncommon among patients 60 years of age and older. MG onset for patients with thymoma is significantly later than that of patients with thymus hyperplasia. Almost all patients with thymoma or thymus hyperplasia develop a generalised form of MG. The presence of a thymus pathology does not significantly affect the electrophysiological test results, clinical symptom severity, frequency of disability or hospitalisation of the patients with MG. Thymectomy in patients with thymoma or thymus hyperplasia has no significant effect on relieving MG symptoms

Intranuclear distribution of Epstein-Barr virus-encoded nuclear antigens EBNA-1, -2, -3 and -5

1991 ◽  
Vol 99 (3) ◽  
pp. 497-502 ◽  
Author(s):  
W.Q. Jiang ◽  
V. Wendel-Hansen ◽  
A. Lundkvist ◽  
N. Ringertz ◽  
G. Klein ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Epstein Barr Virus ◽  
Digital Image Analysis ◽  
Mouse Monoclonal Antibody ◽  
Human Antibody ◽  
Barr Virus ◽  
Nuclear Antigens ◽  
Topographical Analysis ◽  
Epstein Barr ◽  
Nuclear Structures

Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) express at least seven virally encoded proteins. Their functional role, and their relationships to each other and to normal nuclear constituents are virtually unknown. As the first step towards a topographical study, the intranuclear distribution of EBV-encoded nuclear antigens EBNA-1, -2, -3 and -5 (abbreviated E1, E2 etc.) was examined in EBV-transformed LCLs by immunofluorescence and digital image analysis of fluorescence patterns. E1-E3 showed a finely granular distribution. The E2 patterns were virtually identical when comparing indirect staining using an E2-specific mouse monoclonal antibody with anticomplement immunofluorescence using a human antibody, rendered monospecific to E2 by absorption. The E1/E2 patterns showed 32% overlap and the E2/E3 10% overlap in the high overlap category (66.7-100%), while the E2/E2 comparison with two reagents showed 61% overlap in this category. This suggests that E2 and E3 largely appear in different nuclear structures, whereas E1 appears to be randomly distributed with regard to E2. The E5 pattern was radically different from that of E1, E2 and E3. The anti-E5 mouse monoclonal antibody detected 4–10 huge, globular, sharply circumscribed dots, located in dispersed chromatin areas, while the distribution of E1, E2 and E3 showed no obvious relationship to chromatin distribution. The methods described here allow a more refined topographical analysis of the EBNA protein family, mostly in relation to each other, in relation to other nuclear proteins, and with respect to specialized functional domains in interphase chromatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognosis of thymectomy in myasthenia gravis patients with thymus hyperplasia

2016 ◽  
Vol 127 (9) ◽  
pp. 785-789 ◽  
Author(s):  
Jing Yang ◽  
Chanchan Liu ◽  
Tao Li ◽  
Chengyan Li
Keyword(s):  
Myasthenia Gravis ◽  
Thymus Hyperplasia

scholarly journals Autoimmune antibodies to collagen XIII in myasthenia gravis patients

2017 ◽  
Vol 57 (3) ◽  
pp. 506-510 ◽  
Author(s):  
Hongmin Tu ◽  
Ritva Pirskanen-Matell ◽  
Anne Heikkinen ◽  
Tuomo Oikarainen ◽  
Juha Risteli ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Autoimmune Antibodies

Myasthenia gravis with thymus hyperplasia and pure red cell aplasia

2004 ◽  
Vol 224 (1-2) ◽  
pp. 93-95 ◽  
Author(s):  
Yutaka Suto ◽  
Shigeru Araga ◽  
Kenji Sakuma ◽  
Toshiya Nakano ◽  
Kiyomi Ishiga ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Pure Red Cell Aplasia ◽  
Red Cell ◽  
Red Cell Aplasia ◽  
Thymus Hyperplasia

Neuromyelitis optica spectrum disorders in patients with myasthenia gravis: ten new aquaporin-4 antibody positive cases and a review of the literature

2011 ◽  
Vol 18 (8) ◽  
pp. 1135-1143 ◽  
Author(s):  
S Jarius ◽  
F Paul ◽  
D Franciotta ◽  
J de Seze ◽  
C Münch ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Neuromyelitis Optica ◽  
Transverse Myelitis ◽  
Autoimmune Disorders ◽  
Review Of The Literature ◽  
Autoimmune Antibodies ◽  
Devic Syndrome ◽  
History Of ◽  
Caucasian Patients ◽  
Spectrum Disorders

Background: Neuromyelitis optica (NMO, Devic syndrome) and myasthenia gravis (MG) are rare antibody-mediated autoimmune disorders. Concurrent incidence has been reported in only few patients, mostly non-Caucasians. Objective: To report on ten Caucasian patients with NMO spectrum disorders (NMOSD) and MG and to provide a comprehensive review of the literature. Method: Retrospective study. Results: In total, 26 patients (m:f = 1:12; Caucasian in 12) with MG (generalized in 17) and NMOSD (NMO in 21, longitudinally extensive transverse myelitis in five) were identified from the authors’ own files ( n = 10) and the previous literature ( n = 16). MG preceded NMOSD in 24/25 cases (96%). AQP4-Ab were tested in 20 patients and were positive in 17 (85%). Twenty out of 25 patients (80%) had been treated with thymectomy or thymic irradiation, which preceded NMOSD in all cases (median latency, 12 years; range, 0.3–32). At last follow-up, complete remission of MG was reported in 15/22 (68%), and MG was well controlled with pyridostigmine in three. Co-existing autoimmune disorders or autoimmune antibodies were reported in 17 patients. Conclusion: Our study demonstrates that i) AQP4-Ab-positive NMOSD are more commonly associated with MG in Caucasians than previously thought; ii) MG precedes NMOSD in most cases, often by more than a decade; iii) NMOSD almost exclusively occur in females with juvenile or early-onset MG; and iv) MG frequently takes an unusually mild course in patients with NMOSD. A history of thymectomy could be a possible risk factor for the later development of NMOSD. We recommend testing for AQP4-Ab in MG patients presenting with atypical motor or optic symptoms.

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