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

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 diagnost...

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Main Authors: E. M. Klimova, D. V. Minuchin, L. A. Drozdova, E. V. Lavinskaya, T. I. Kordon, Y. V. Kalashnykova
Format: Article
Language:English
Published: Oles Honchar Dnipro National University 2018-07-01
Series:Regulatory Mechanisms in Biosystems
Subjects:
Online Access:https://medicine.dp.ua/index.php/med/article/view/489
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author E. M. Klimova
D. V. Minuchin
L. A. Drozdova
E. V. Lavinskaya
T. I. Kordon
Y. V. Kalashnykova
author_facet E. M. Klimova
D. V. Minuchin
L. A. Drozdova
E. V. Lavinskaya
T. I. Kordon
Y. V. Kalashnykova
author_sort E. M. Klimova
collection DOAJ
description 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.
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spelling doaj.art-746c2ac17a8b432ebd9052831fcc72e12022-12-22T02:39:02ZengOles Honchar Dnipro National UniversityRegulatory Mechanisms in Biosystems2519-85212520-25882018-07-019456156710.15421/021884489Features of self-tolerance loss in patients with different clinical phenotypes of myastheniaE. M. Klimova0D. V. Minuchin1L. A. Drozdova2E. V. Lavinskaya3T. I. Kordon4Y. V. Kalashnykova5Zaycev V. T. Institute of General and Urgent Surgery of National Academy of Medical Sciences of UkraineKharkiv National Medical UniversityZaycev V. T. Institute of General and Urgent Surgery of National Academy of Medical Sciences of UkraineZaycev V. T. Institute of General and Urgent Surgery of National Academy of Medical Sciences of UkraineZaycev V. T. Institute of General and Urgent Surgery of National Academy of Medical Sciences of UkraineZaycev V. T. Institute of General and Urgent Surgery of National Academy of Medical Sciences of UkraineThe 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.https://medicine.dp.ua/index.php/med/article/view/489clinical myasthenia phenotypes; autoantibody spectrum; regulatory t lymphocytes; co-stimulating molecules; acute phase proteins
spellingShingle E. M. Klimova
D. V. Minuchin
L. A. Drozdova
E. V. Lavinskaya
T. I. Kordon
Y. V. Kalashnykova
Features of self-tolerance loss in patients with different clinical phenotypes of myasthenia
Regulatory Mechanisms in Biosystems
clinical myasthenia phenotypes; autoantibody spectrum; regulatory t lymphocytes; co-stimulating molecules; acute phase proteins
title Features of self-tolerance loss in patients with different clinical phenotypes of myasthenia
title_full Features of self-tolerance loss in patients with different clinical phenotypes of myasthenia
title_fullStr Features of self-tolerance loss in patients with different clinical phenotypes of myasthenia
title_full_unstemmed Features of self-tolerance loss in patients with different clinical phenotypes of myasthenia
title_short Features of self-tolerance loss in patients with different clinical phenotypes of myasthenia
title_sort features of self tolerance loss in patients with different clinical phenotypes of myasthenia
topic clinical myasthenia phenotypes; autoantibody spectrum; regulatory t lymphocytes; co-stimulating molecules; acute phase proteins
url https://medicine.dp.ua/index.php/med/article/view/489
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