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Stereotypic T cell receptor clonotypes in the thymus and peripheral blood of Myasthenia gravis patients

Authors
 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 
Citation
 HELIYON, Vol.10(4) : e26663, 2024-02 
Journal Title
HELIYON
Issue Date
2024-02
Keywords
Acetylcholine receptor ; Myasthenia gravis ; T cell receptor repertoire ; Thymus
Abstract
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.
Files in This Item:
T202402398.pdf Download
DOI
10.1016/j.heliyon.2024.e26663
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seung Woo(김승우) ORCID logo https://orcid.org/0000-0002-5621-0811
Kim, Ha Eun(김하은)
Park, Byung Jo(박병조)
Shin, Ha Young(신하영) ORCID logo https://orcid.org/0000-0002-4408-8265
Yang, Young Ho(양영호)
Lee, Jin Gu(이진구)
Lee, Chang Young(이창영)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/199116
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