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Pathogenetic Significance of Fetal-Type Acetylcholine Receptors on Thymic Myoid Cells in Myasthenia Gravis

To investigate the role of thymic myoid cells in the pathogenesis of myasthenia gravis (MG), mRNA of nonneoplastic thymuses from eight MG patients was analyzed by dot blot hybridization for the occurrence of acetylcholine receptor (AChR) subunit transcripts, using the five AChR-subunit cDNAs (alpha,...

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Autores principales: Geuder, Kerstin I., Marx, Alexander, Witzemann, Veit, Schalke, Berthold, Toyka, Klaus, Kirchner, Thomas, Müller-Hermelink, Hans-Konrad
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 1992
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275847/
https://www.ncbi.nlm.nih.gov/pubmed/1643420
http://dx.doi.org/10.1155/1992/40576
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author Geuder, Kerstin I.
Marx, Alexander
Witzemann, Veit
Schalke, Berthold
Toyka, Klaus
Kirchner, Thomas
Müller-Hermelink, Hans-Konrad
author_facet Geuder, Kerstin I.
Marx, Alexander
Witzemann, Veit
Schalke, Berthold
Toyka, Klaus
Kirchner, Thomas
Müller-Hermelink, Hans-Konrad
author_sort Geuder, Kerstin I.
collection PubMed
description To investigate the role of thymic myoid cells in the pathogenesis of myasthenia gravis (MG), mRNA of nonneoplastic thymuses from eight MG patients was analyzed by dot blot hybridization for the occurrence of acetylcholine receptor (AChR) subunit transcripts, using the five AChR-subunit cDNAs (alpha, beta, gamma, delta, and epsilon) as probes. Attention was particularly paid to the gamma- and epsilon-subunit transcripts that specify fetal- or adult-type AChR. In all eight thymuses, transcripts of the alpha-, beta-, gamma-, and delta-subunit genes were detected. Relative autoradiographic signal intensities correlated with the frequencies of thymic myoid cells as determined by immunostaining with anti-AChR monoclonal antibodies. In only one of these thymuses were transcripts of the epsilon-subunit gene detected in addition to those of the other subunit genes. Four MG-associated thymomas without myoid cells were devoid of any AChR-subunit mRNA. Our findings imply that fetal-type AChR is expressed in MG thymuses as a rule, whereas adult-type AChR is coexpressed with it only in a minority of cases. A similar pattern of cotranscription is known to occur at certain stages of muscle development, and can be found in human rhabdomyosarcomas with an intermediate stage of myogenesis. Because the serum autoantibodies of MG patients exhibit preferential reactivity with fetal AChRs, the presence of fetal AChRs in the thymus provides circumstantial evidence for an active involvement of thymic myoid cells in the autoimmune process.
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spelling pubmed-22758472008-03-31 Pathogenetic Significance of Fetal-Type Acetylcholine Receptors on Thymic Myoid Cells in Myasthenia Gravis Geuder, Kerstin I. Marx, Alexander Witzemann, Veit Schalke, Berthold Toyka, Klaus Kirchner, Thomas Müller-Hermelink, Hans-Konrad Dev Immunol Research Article To investigate the role of thymic myoid cells in the pathogenesis of myasthenia gravis (MG), mRNA of nonneoplastic thymuses from eight MG patients was analyzed by dot blot hybridization for the occurrence of acetylcholine receptor (AChR) subunit transcripts, using the five AChR-subunit cDNAs (alpha, beta, gamma, delta, and epsilon) as probes. Attention was particularly paid to the gamma- and epsilon-subunit transcripts that specify fetal- or adult-type AChR. In all eight thymuses, transcripts of the alpha-, beta-, gamma-, and delta-subunit genes were detected. Relative autoradiographic signal intensities correlated with the frequencies of thymic myoid cells as determined by immunostaining with anti-AChR monoclonal antibodies. In only one of these thymuses were transcripts of the epsilon-subunit gene detected in addition to those of the other subunit genes. Four MG-associated thymomas without myoid cells were devoid of any AChR-subunit mRNA. Our findings imply that fetal-type AChR is expressed in MG thymuses as a rule, whereas adult-type AChR is coexpressed with it only in a minority of cases. A similar pattern of cotranscription is known to occur at certain stages of muscle development, and can be found in human rhabdomyosarcomas with an intermediate stage of myogenesis. Because the serum autoantibodies of MG patients exhibit preferential reactivity with fetal AChRs, the presence of fetal AChRs in the thymus provides circumstantial evidence for an active involvement of thymic myoid cells in the autoimmune process. Hindawi Publishing Corporation 1992 /pmc/articles/PMC2275847/ /pubmed/1643420 http://dx.doi.org/10.1155/1992/40576 Text en Copyright © 1992 Hindawi Publishing Corporation. http://creativecommons.org/licenses/by/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Geuder, Kerstin I.
Marx, Alexander
Witzemann, Veit
Schalke, Berthold
Toyka, Klaus
Kirchner, Thomas
Müller-Hermelink, Hans-Konrad
Pathogenetic Significance of Fetal-Type Acetylcholine Receptors on Thymic Myoid Cells in Myasthenia Gravis
title Pathogenetic Significance of Fetal-Type Acetylcholine Receptors on Thymic Myoid Cells in Myasthenia Gravis
title_full Pathogenetic Significance of Fetal-Type Acetylcholine Receptors on Thymic Myoid Cells in Myasthenia Gravis
title_fullStr Pathogenetic Significance of Fetal-Type Acetylcholine Receptors on Thymic Myoid Cells in Myasthenia Gravis
title_full_unstemmed Pathogenetic Significance of Fetal-Type Acetylcholine Receptors on Thymic Myoid Cells in Myasthenia Gravis
title_short Pathogenetic Significance of Fetal-Type Acetylcholine Receptors on Thymic Myoid Cells in Myasthenia Gravis
title_sort pathogenetic significance of fetal-type acetylcholine receptors on thymic myoid cells in myasthenia gravis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275847/
https://www.ncbi.nlm.nih.gov/pubmed/1643420
http://dx.doi.org/10.1155/1992/40576
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