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Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease
BACKGROUND AND OBJECTIVES: To investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact. METHODS: Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474506/ https://www.ncbi.nlm.nih.gov/pubmed/34561276 http://dx.doi.org/10.1212/NXI.0000000000001087 |
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author | Yamamoto, Yohei Matsui, Naoko Uzawa, Akiyuki Ozawa, Yukiko Kanai, Tetsuya Oda, Fumiko Kondo, Hiroyuki Ohigashi, Izumi Takizawa, Hiromitsu Kondo, Kazuya Sugano, Mikio Kitaichi, Takashi Hata, Hiroki Kaji, Ryuji Kuwabara, Satoshi Yamamura, Takashi Izumi, Yuishin |
author_facet | Yamamoto, Yohei Matsui, Naoko Uzawa, Akiyuki Ozawa, Yukiko Kanai, Tetsuya Oda, Fumiko Kondo, Hiroyuki Ohigashi, Izumi Takizawa, Hiromitsu Kondo, Kazuya Sugano, Mikio Kitaichi, Takashi Hata, Hiroki Kaji, Ryuji Kuwabara, Satoshi Yamamura, Takashi Izumi, Yuishin |
author_sort | Yamamoto, Yohei |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: To investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact. METHODS: Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19(+)B220(high) thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed. Immunologic values were compared, and correlations between relevant values and clinical parameters were evaluated. RESULTS: The frequencies of circulating and intrathymic plasmablasts were significantly higher in patients with MG than controls. On the other hand, the frequency of CD19(+)B220(high) thymic B cells was not increased in MG thymus. We observed a significant increase in CXCR5 expression on plasmablasts in MG thymus and an increased frequency of intrathymic plasmablasts that was correlated with preoperative disease activity. The frequency of intrathymic Tfh cells was significantly lower in patients who received immunosuppressive (IS) therapy than those without IS therapy. However, there was no significant difference in the frequency of intrathymic plasmablasts irrespective of IS therapy. DISCUSSION: Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG. |
format | Online Article Text |
id | pubmed-8474506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-84745062021-09-27 Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease Yamamoto, Yohei Matsui, Naoko Uzawa, Akiyuki Ozawa, Yukiko Kanai, Tetsuya Oda, Fumiko Kondo, Hiroyuki Ohigashi, Izumi Takizawa, Hiromitsu Kondo, Kazuya Sugano, Mikio Kitaichi, Takashi Hata, Hiroki Kaji, Ryuji Kuwabara, Satoshi Yamamura, Takashi Izumi, Yuishin Neurol Neuroimmunol Neuroinflamm Article BACKGROUND AND OBJECTIVES: To investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact. METHODS: Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19(+)B220(high) thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed. Immunologic values were compared, and correlations between relevant values and clinical parameters were evaluated. RESULTS: The frequencies of circulating and intrathymic plasmablasts were significantly higher in patients with MG than controls. On the other hand, the frequency of CD19(+)B220(high) thymic B cells was not increased in MG thymus. We observed a significant increase in CXCR5 expression on plasmablasts in MG thymus and an increased frequency of intrathymic plasmablasts that was correlated with preoperative disease activity. The frequency of intrathymic Tfh cells was significantly lower in patients who received immunosuppressive (IS) therapy than those without IS therapy. However, there was no significant difference in the frequency of intrathymic plasmablasts irrespective of IS therapy. DISCUSSION: Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG. Lippincott Williams & Wilkins 2021-09-24 /pmc/articles/PMC8474506/ /pubmed/34561276 http://dx.doi.org/10.1212/NXI.0000000000001087 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Article Yamamoto, Yohei Matsui, Naoko Uzawa, Akiyuki Ozawa, Yukiko Kanai, Tetsuya Oda, Fumiko Kondo, Hiroyuki Ohigashi, Izumi Takizawa, Hiromitsu Kondo, Kazuya Sugano, Mikio Kitaichi, Takashi Hata, Hiroki Kaji, Ryuji Kuwabara, Satoshi Yamamura, Takashi Izumi, Yuishin Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease |
title | Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease |
title_full | Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease |
title_fullStr | Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease |
title_full_unstemmed | Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease |
title_short | Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease |
title_sort | intrathymic plasmablasts are affected in patients with myasthenia gravis with active disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474506/ https://www.ncbi.nlm.nih.gov/pubmed/34561276 http://dx.doi.org/10.1212/NXI.0000000000001087 |
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