Unravelling the TCRβ repertoire: a key to unlocking the immunopathogenesis and precision medicine in SLE

Objectives SLE is a multifaceted autoimmune disorder with a complex pathogenesis involving genetic, environmental and hormonal factors, which converge on immune dysregulation. The T cell receptor (TCR) repertoire’s role in SLE has garnered significant interest due to its potential in both diagnostic...

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Main Authors: Qiao Zhou, Li Zeng, Zhixin Zhang, Jian Liu, Yichen Zhang, Yang An, Lijing Yang, Tianzuo Lan, Pengming He, Xueping Wen, Shaoping Deng
Format: Article
Language:English
Published: BMJ Publishing Group 2025-01-01
Series:Lupus Science and Medicine
Online Access:https://lupus.bmj.com/content/12/1/e001384.full
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author Qiao Zhou
Li Zeng
Zhixin Zhang
Jian Liu
Yichen Zhang
Yang An
Lijing Yang
Tianzuo Lan
Pengming He
Xueping Wen
Shaoping Deng
author_facet Qiao Zhou
Li Zeng
Zhixin Zhang
Jian Liu
Yichen Zhang
Yang An
Lijing Yang
Tianzuo Lan
Pengming He
Xueping Wen
Shaoping Deng
author_sort Qiao Zhou
collection DOAJ
description Objectives SLE is a multifaceted autoimmune disorder with a complex pathogenesis involving genetic, environmental and hormonal factors, which converge on immune dysregulation. The T cell receptor (TCR) repertoire’s role in SLE has garnered significant interest due to its potential in both diagnostics and therapeutics. Our study aimed to delineate the variances in the TCRβ repertoire between patients with SLE and healthy individuals, correlating these differences with the severity and subtypes of SLE.Methods We conducted an analysis of blood samples from 50 treatment-naive patients with SLE and 50 healthy donors, employing RNA extraction, high-throughput sequencing and subsequent bioinformatics analysis.Results Our findings revealed significant alterations in TRBV and TRBJ gene usage frequencies, indicative of a skewed TCR repertoire in patients with SLE. Notably, nine hub TRBV genes were identified as potential biomarkers for SLE with high diagnostic accuracy. Furthermore, we observed a reduction in TCR diversity, characterised by a lower diversity 50 value and increased clonal expansion, which correlated with disease severity.Conclusions The TCRβ repertoire is significantly altered in SLE, with potential implications for diagnostics and therapeutics. The identified hub genes may serve as novel biomarkers for SLE, and the findings contribute to the understanding of the immunopathogenesis of the disease.
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issn 2053-8790
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publishDate 2025-01-01
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spelling doaj-art-c46f9c7f3dc3472290b4b7903cd145e02025-01-21T12:00:10ZengBMJ Publishing GroupLupus Science and Medicine2053-87902025-01-0112110.1136/lupus-2024-001384Unravelling the TCRβ repertoire: a key to unlocking the immunopathogenesis and precision medicine in SLEQiao Zhou0Li Zeng1Zhixin Zhang2Jian Liu3Yichen Zhang4Yang An5Lijing Yang6Tianzuo Lan7Pengming He8Xueping Wen9Shaoping Deng10Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People`s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Neurology, Sichuan Provincial People`s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Technology, Chengdu ExAb Biotechnology, Ltd, Chengdu, ChinaDepartment of Rheumatology and Immunology, Sichuan Provincial People`s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaSecond Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, ChinaSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Rheumatology, The First People’s Hospital of Guiyang, Guiyang, Guizhou Province, ChinaDepartment of Technology, Chengdu ExAb Biotechnology, Ltd, Chengdu, ChinaDepartment of Technology, Chengdu ExAb Biotechnology, Ltd, Chengdu, ChinaSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaObjectives SLE is a multifaceted autoimmune disorder with a complex pathogenesis involving genetic, environmental and hormonal factors, which converge on immune dysregulation. The T cell receptor (TCR) repertoire’s role in SLE has garnered significant interest due to its potential in both diagnostics and therapeutics. Our study aimed to delineate the variances in the TCRβ repertoire between patients with SLE and healthy individuals, correlating these differences with the severity and subtypes of SLE.Methods We conducted an analysis of blood samples from 50 treatment-naive patients with SLE and 50 healthy donors, employing RNA extraction, high-throughput sequencing and subsequent bioinformatics analysis.Results Our findings revealed significant alterations in TRBV and TRBJ gene usage frequencies, indicative of a skewed TCR repertoire in patients with SLE. Notably, nine hub TRBV genes were identified as potential biomarkers for SLE with high diagnostic accuracy. Furthermore, we observed a reduction in TCR diversity, characterised by a lower diversity 50 value and increased clonal expansion, which correlated with disease severity.Conclusions The TCRβ repertoire is significantly altered in SLE, with potential implications for diagnostics and therapeutics. The identified hub genes may serve as novel biomarkers for SLE, and the findings contribute to the understanding of the immunopathogenesis of the disease.https://lupus.bmj.com/content/12/1/e001384.full
spellingShingle Qiao Zhou
Li Zeng
Zhixin Zhang
Jian Liu
Yichen Zhang
Yang An
Lijing Yang
Tianzuo Lan
Pengming He
Xueping Wen
Shaoping Deng
Unravelling the TCRβ repertoire: a key to unlocking the immunopathogenesis and precision medicine in SLE
Lupus Science and Medicine
title Unravelling the TCRβ repertoire: a key to unlocking the immunopathogenesis and precision medicine in SLE
title_full Unravelling the TCRβ repertoire: a key to unlocking the immunopathogenesis and precision medicine in SLE
title_fullStr Unravelling the TCRβ repertoire: a key to unlocking the immunopathogenesis and precision medicine in SLE
title_full_unstemmed Unravelling the TCRβ repertoire: a key to unlocking the immunopathogenesis and precision medicine in SLE
title_short Unravelling the TCRβ repertoire: a key to unlocking the immunopathogenesis and precision medicine in SLE
title_sort unravelling the tcrβ repertoire a key to unlocking the immunopathogenesis and precision medicine in sle
url https://lupus.bmj.com/content/12/1/e001384.full
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