Stereotypic T cell receptor clonotypes in the thymus and peripheral blood of Myasthenia gravis patients
Myasthenia Gravis (MG) patients with anti-acetylcholine receptor (AChR) antibodies frequently show hyperplastic thymi with ectopic germinal centers, where autoreactive B cells proliferate with the aid of T cells. In this study, thymus and peripheral blood (PB) samples were collected from ten AChR an...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402402694X |
| _version_ | 1797267602580439040 |
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| author | Yonghee Lee Seung Woo Kim Eunjae Lee Ha Young Shin MinGi Kim Chang Young Lee Byung Jo Park Ha Eun Kim Young Ho Yang Jinny Choi Soyeon Ju Jungheum Park Namphil Kim Jaewon Choi Jin Gu Lee Sunghoon Kwon Junho Chung |
| author_facet | Yonghee Lee Seung Woo Kim Eunjae Lee Ha Young Shin MinGi Kim Chang Young Lee Byung Jo Park Ha Eun Kim Young Ho Yang Jinny Choi Soyeon Ju Jungheum Park Namphil Kim Jaewon Choi Jin Gu Lee Sunghoon Kwon Junho Chung |
| author_sort | Yonghee Lee |
| collection | DOAJ |
| description | Myasthenia Gravis (MG) patients with anti-acetylcholine receptor (AChR) antibodies frequently show hyperplastic thymi with ectopic germinal centers, where autoreactive B cells proliferate with the aid of T cells. In this study, thymus and peripheral blood (PB) samples were collected from ten AChR antibody-positive MG patients. T cell receptor (TCR) repertoires were analyzed using next-generation sequencing (NGS), and compared with that of an age and sex matched control group generated from a public database. Certain V genes and VJ gene recombination pairs were significantly upregulated in the TCR chains of αβ-T cells in the PB of MG patients compared to the control group. Furthermore, the TCR chains found in the thymi of MG patients had a weighted distribution to longer CDR3 lengths when compared to the PB of MG patients, and the TCR beta chains (TRB) in the MG group's PB showed increased clonality encoded by one upregulated V gene. When TRB sequences were sub-divided into groups based on their CDR3 lengths, certain groups showed decreased clonality in the MG group's PB compared to the control group's PB. Finally, we demonstrated that stereotypic MG patient-specific TCR clonotypes co-exist in both the PB and thymi at a much higher frequency than that of the clonotypes confined to the PB. These results strongly suggest the existence of a biased T cell-mediated immune response in MG patients, as observed in other autoimmune diseases. |
| first_indexed | 2024-03-07T22:54:15Z |
| format | Article |
| id | doaj.art-6023900e9a2f488bb6526563ca72158c |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-25T01:19:12Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-6023900e9a2f488bb6526563ca72158c2024-03-09T09:28:49ZengElsevierHeliyon2405-84402024-02-01104e26663Stereotypic T cell receptor clonotypes in the thymus and peripheral blood of Myasthenia gravis patientsYonghee Lee0Seung Woo Kim1Eunjae Lee2Ha Young Shin3MinGi Kim4Chang Young Lee5Byung Jo Park6Ha Eun Kim7Young Ho Yang8Jinny Choi9Soyeon Ju10Jungheum Park11Namphil Kim12Jaewon Choi13Jin Gu Lee14Sunghoon Kwon15Junho Chung16Department of Electrical and Computer Engineering, Seoul National University, Seoul 08826, Republic of KoreaDepartment of Neurology, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDepartment of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Neurology, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDepartment of Neurology, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDepartment of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDepartment of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDepartment of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDepartment of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaCancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Electrical and Computer Engineering, Seoul National University, Seoul 08826, Republic of KoreaInterdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea; Integrated Major in Innovative Medical Science, Seoul National University, Seoul 08826, Republic of KoreaDepartment of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Corresponding author. Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.Department of Electrical and Computer Engineering, Seoul National University, Seoul 08826, Republic of Korea; Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea; Bio-MAX Institute, Seoul National University, Seoul 08826, Republic of Korea; Corresponding author. Department of Electrical and Computer Engineering, Seoul National University, Seoul 08826, Republic of Korea.Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Interdisciplinary Program in Cancer Biology Major, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Corresponding author. Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.Myasthenia Gravis (MG) patients with anti-acetylcholine receptor (AChR) antibodies frequently show hyperplastic thymi with ectopic germinal centers, where autoreactive B cells proliferate with the aid of T cells. In this study, thymus and peripheral blood (PB) samples were collected from ten AChR antibody-positive MG patients. T cell receptor (TCR) repertoires were analyzed using next-generation sequencing (NGS), and compared with that of an age and sex matched control group generated from a public database. Certain V genes and VJ gene recombination pairs were significantly upregulated in the TCR chains of αβ-T cells in the PB of MG patients compared to the control group. Furthermore, the TCR chains found in the thymi of MG patients had a weighted distribution to longer CDR3 lengths when compared to the PB of MG patients, and the TCR beta chains (TRB) in the MG group's PB showed increased clonality encoded by one upregulated V gene. When TRB sequences were sub-divided into groups based on their CDR3 lengths, certain groups showed decreased clonality in the MG group's PB compared to the control group's PB. Finally, we demonstrated that stereotypic MG patient-specific TCR clonotypes co-exist in both the PB and thymi at a much higher frequency than that of the clonotypes confined to the PB. These results strongly suggest the existence of a biased T cell-mediated immune response in MG patients, as observed in other autoimmune diseases.http://www.sciencedirect.com/science/article/pii/S240584402402694XMyasthenia gravisAcetylcholine receptorT cell receptor repertoireThymus |
| spellingShingle | Yonghee Lee Seung Woo Kim Eunjae Lee Ha Young Shin MinGi Kim Chang Young Lee Byung Jo Park Ha Eun Kim Young Ho Yang Jinny Choi Soyeon Ju Jungheum Park Namphil Kim Jaewon Choi Jin Gu Lee Sunghoon Kwon Junho Chung Stereotypic T cell receptor clonotypes in the thymus and peripheral blood of Myasthenia gravis patients Heliyon Myasthenia gravis Acetylcholine receptor T cell receptor repertoire Thymus |
| title | Stereotypic T cell receptor clonotypes in the thymus and peripheral blood of Myasthenia gravis patients |
| title_full | Stereotypic T cell receptor clonotypes in the thymus and peripheral blood of Myasthenia gravis patients |
| title_fullStr | Stereotypic T cell receptor clonotypes in the thymus and peripheral blood of Myasthenia gravis patients |
| title_full_unstemmed | Stereotypic T cell receptor clonotypes in the thymus and peripheral blood of Myasthenia gravis patients |
| title_short | Stereotypic T cell receptor clonotypes in the thymus and peripheral blood of Myasthenia gravis patients |
| title_sort | stereotypic t cell receptor clonotypes in the thymus and peripheral blood of myasthenia gravis patients |
| topic | Myasthenia gravis Acetylcholine receptor T cell receptor repertoire Thymus |
| url | http://www.sciencedirect.com/science/article/pii/S240584402402694X |
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