The start of an autoimmune disease: idiotypic network during early progression of myasthenia gravis

1988 ◽  
Vol 139 (6) ◽  
pp. 633-643 ◽  
Author(s):  
A.K. Lefvert
Keyword(s):  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Idiotypic Network ◽  
Early Progression

scholarly journals Rapamycin alleviates inflammation and muscle weakness, while altering the Treg/Th17 balance in a rat model of myasthenia gravis

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Feng Jing ◽  
Fei Yang ◽  
Fang Cui ◽  
Zhaohui Chen ◽  
Li Ling ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Rat Model ◽  
Th17 Cells ◽  
Mortality Rates ◽  
The Novel ◽  
Muscular Weakness ◽  
Body Weights ◽  
Experimental Autoimmune

Myasthenia gravis (MG) is an autoimmune disease commonly treated with immunosuppressants. We evaluated the novel immunosuppressant, rapamycin (RAPA), in a rat model of experimental autoimmune MG (EAMG). Mortality rates in the RAPA (12%) were significantly down compared with the EAMG (88%) or cyclophosphamide (CTX) (68%) intervention groups. Muscular weakness decreased after both RAPA and CTX treatment. However, Lennon scores were lower (1.74 ± 0.49, 3.39 ± 0.21, and 3.81 ± 0.22 in RAPA, CTX, and EAMG groups, respectively), and body weights (203.12 ± 4.13 g, 179.23 ± 2.13 g, and 180.13 ± 5.13 g in RAPA, CTX, and EAMG groups, respectively) were significantly higher, only in the RAPA group. The proportion of regulatory T cells (Treg) significantly increased, while that of Th17 cells significantly decreased in the RAPA group compared with the EAMG group. In comparison, CTX intervention resulted in increased Th17 but significantly decreased Tregs. Hence, RAPA can be more effectively used in comparison with CTX to treat MG, with an efficacy higher than that of CTX. In addition, our results suggest RAPA’s efficacy in alleviating symptoms of MG stems from its ability to correct the Treg/Th17 imbalance observed in MG.

scholarly journals Functional monovalency amplifies the pathogenicity of anti-MuSK IgG4 in myasthenia gravis

2021 ◽  
Vol 118 (13) ◽  
pp. e2020635118
Author(s):  
Dana L. E. Vergoossen ◽  
Jaap J. Plomp ◽  
Christoph Gstöttner ◽  
Yvonne E. Fillié-Grijpma ◽  
Roy Augustinus ◽  
...  
Keyword(s):  
Stochastic Process ◽  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Binding Sites ◽  
Antiinflammatory Activity ◽  
Autoimmune Response ◽  
Cross Link ◽  
Muscle Specific Kinase ◽  
Opposing Effects

Human immunoglobulin (Ig) G4 usually displays antiinflammatory activity, and observations of IgG4 autoantibodies causing severe autoimmune disorders are therefore poorly understood. In blood, IgG4 naturally engages in a stochastic process termed “Fab-arm exchange” in which unrelated IgG4s exchange half-molecules continuously. The resulting IgG4 antibodies are composed of two different binding sites, thereby acquiring monovalent binding and inability to cross-link for each antigen recognized. Here, we demonstrate that this process amplifies autoantibody pathogenicity in a classic IgG4-mediated autoimmune disease: muscle-specific kinase (MuSK) myasthenia gravis. In mice, monovalent anti-MuSK IgG4s caused rapid and severe myasthenic muscle weakness, whereas the same antibodies in their parental bivalent form were less potent or did not induce a phenotype. Mechanistically this could be explained by opposing effects on MuSK signaling. Isotype switching to IgG4 in an autoimmune response thereby may be a critical step in the development of disease. Our study establishes functional monovalency as a pathogenic mechanism in IgG4-mediated autoimmune disease and potentially other disorders.

scholarly journals Thymocyte Fas Expression Is Dysregulated in Myasthenia Gravis Patients With Anti-Acetylcholine Receptor Antibody

Blood ◽  
1997 ◽  
Vol 89 (9) ◽  
pp. 3287-3295 ◽  
Author(s):  
Nathalie Moulian ◽  
Jocelyne Bidault ◽  
Frédérique Truffault ◽  
Ana Maria Yamamoto ◽  
Philippe Levasseur ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Acetylcholine Receptor ◽  
Peripheral Blood ◽  
Proliferative Response ◽  
Peripheral Blood Lymphocytes ◽  
Autoimmune Response ◽  
Human Autoimmune Disease ◽  
Autoreactive Cells ◽  
Anti Acetylcholine

Abstract Myasthenia gravis (MG) is a human autoimmune disease mediated by anti-acetylcholine receptor (AChR) antibodies. The thymus is probably the site where the autoimmune response is triggered and maintained. Recent reports have linked various autoimmune disease with defective Fas expression. We thus analyzed Fas expression in thymocytes and peripheral blood lymphocytes (PBL) from MG patients. The proportion of a thymocyte subpopulation with strong Fas expression (Fashi) was markedly enhanced in MG patients with anti-AChR antibodies (P < .0003, compared with controls). In this group of patients, the proportion of CD4+Fashi and CD4+CD8+Fashi thymocytes were significantly increased (P < .002 for both subsets). Fashi thymocytes were enriched in activated cells and showed intermediate CD3 expression. They were preferentially Vβ5.1-expressing cells, previously shown to be enriched in potentially autoreactive cells. The proliferative response of thymocytes from MG patients to peptides from the AChR was abolished after depletion of Fashi cells. Fashi thymocytes were sensitive to an agonistic anti-Fas antibody. In peripheral blood, Fashi lymphocytes proportion was not significantly modified in MG patients whatever their anti-AChR antibody titer, compared with controls. Altogether, these results indicate that Fashi thymocytes, which accumulate in MG patients with anti-AChR antibodies, could be involved in the autoimmune response that targets the AChR.

scholarly journals Functional defect of regulatory CD4+CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 735-741 ◽  
Author(s):  
Anna Balandina ◽  
Sandrine Lécart ◽  
Philippe Dartevelle ◽  
Abdelhadi Saoudi ◽  
Sonia Berrih-Aknin
Keyword(s):  
T Cells ◽  
T Cell ◽  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Cell Function ◽  
Critical Role ◽  
Treg Cells ◽  
Regulatory Function ◽  
Phenotypic Analysis ◽  
Functional Defect

AbstractThymus-derived CD4+CD25+ regulatory T (Treg) cells are essential for the maintenance of immunologic self-tolerance. Despite their critical role in the active suppression of experimental autoimmune disorders, little is known about their involvement in human autoimmune diseases. Myasthenia gravis (MG) is a CD4+ T cell–dependent autoimmune disease and the thymus is assumed to be the initiation site. To identify possible defects in the Treg cells in MG, we analyzed CD4+CD25+ cells in thymi from patients with MG compared to those from healthy subjects. We found a normal CD4+CD25+ number but a severe functional defect in their regulatory activity together with a decreased expression of the transcription factor, Foxp3, which is essential for T-cell regulatory function. The phenotypic analysis of CD4+CD25+ thymocytes revealed an increased number of activated effector cells with strong Fas expression in patients with MG. However, whatever their level of Fas, CD4+CD25+ thymocytes from patients with MG remained unable to suppress the proliferation of responding cells, indicating that the impaired Treg cell function is not due to contamination by activated effector T cells. These data are the first to demonstrate a severe functional impairment of thymic Treg cells in MG, which could contribute to the onset of this autoimmune disease.

scholarly journals Psychopharmacology in myasthenia gravis patients with focus on depression

2019 ◽  
Vol 7 (8) ◽  
pp. 3230
Author(s):  
Ida Bagus Gede Wisnu Wardhana ◽  
Anak Ayu Sri Wahyuni ◽  
Komang Arimbawa
Keyword(s):  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Side Effect ◽  
Brain Function ◽  
Adequate Treatment ◽  
Psychological Mechanisms

Myasthenia gravis is an autoimmune disease with a potential to disrupt brain function and cause depression as a result of the disease itself or treatment side effect. Some biological and psychological mechanisms have been proposed for the correlations between myasthenia gravis and depression. Depression might present in patients myasthenia gravis, and it might complicate the course of the disease. Adequate treatment might not only improve the depression but might also impact the myasthenia gravis in general.

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