Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome
Summary: Background: Primary Sjogren's syndrome (SS) is a chronic inflammatory disease with unknown aetiology. Although clonal expansion of autoreactive T cells has been identified in patients with SS, the clinical correlation of T-cell receptor (TCR) variance in SS remains unclear. Methods: T...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396422004340 |
| _version_ | 1798003190755491840 |
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| author | Chenyang Lu Xuenan Pi Wangdong Xu Pingying Qing Honghu Tang Yanhong Li Yi Zhao Xiao Liu Huairong Tang Yi Liu |
| author_facet | Chenyang Lu Xuenan Pi Wangdong Xu Pingying Qing Honghu Tang Yanhong Li Yi Zhao Xiao Liu Huairong Tang Yi Liu |
| author_sort | Chenyang Lu |
| collection | DOAJ |
| description | Summary: Background: Primary Sjogren's syndrome (SS) is a chronic inflammatory disease with unknown aetiology. Although clonal expansion of autoreactive T cells has been identified in patients with SS, the clinical correlation of T-cell receptor (TCR) variance in SS remains unclear. Methods: TCRβ repertoire sequencing was performed on 260 SS patients with 3-6 months of follow-up in a cohort study to dynamically assess the characteristics of TCR diversity and their clinical significance. Findings: We found that SS patients had lower TCR diversity, but higher frequency of public clones than healthy controls (HCs). Significant differences were identified in the usage of the variable (V) gene, joining (J) gene, and V-J pairing between SS and HCs. Eighteen SS-associated clones were identified, showing a high sensitivity and specificity for disease classification. TCR diversity was correlated with the presence of dental caries, thrombocytopenia, hepatocholangeitis, antinuclear antibody, anti-SSA/SSB, and hypergammaglobulinemia but not with disease course, number of relapses, arthritis, rheumatoid factor, hypocomplementemia or disease activity defined by SSDAI. During follow-up, the TCR abnormalities remained, represented by more altered V/J usage and higher frequencies of SS-associated clones. Among SS patients, the sensitive subgroup had increased TCR diversity after treatment. Eighty-five SS-sensitivity associated TCRs were identified and used for sensitivity classification by cross validation with high specificity and sensitivity. Interpretation: These results demonstrate that the TCR repertoire could provide insights into the disease status and prognosis in SS and other autoimmune diseases. Funding: This study was funded by the National Key Research and Development Program of China (2016YFC0906201), Sichuan Science and Technology Program (2020YJ0223), and the 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD18015). |
| first_indexed | 2024-04-11T12:05:28Z |
| format | Article |
| id | doaj.art-7bb07a85633d405e91e06783f9dd9a3d |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-11T12:05:28Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-7bb07a85633d405e91e06783f9dd9a3d2022-12-22T04:24:45ZengElsevierEBioMedicine2352-39642022-10-0184104252Clinical significance of T cell receptor repertoire in primary Sjogren's syndromeChenyang Lu0Xuenan Pi1Wangdong Xu2Pingying Qing3Honghu Tang4Yanhong Li5Yi Zhao6Xiao Liu7Huairong Tang8Yi Liu9Laboratory of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, ChinaNational Frontier Center of Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Evidence-Based Medicine, Southwest Medical University, Luzhou, ChinaDepartment of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, ChinaLaboratory of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, ChinaBGI-Shenzhen, Shenzhen 518083, China; Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaHealth Management Center, West China Hospital of Sichuan University, Chengdu 610041, China; Corresponding author at: No.37, Guoxue Alley, Wuhou District, Chengdu 610041, China.Laboratory of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China; Corresponding author at: No.37, Guoxue Alley, Wuhou District, Chengdu 610041, China.Summary: Background: Primary Sjogren's syndrome (SS) is a chronic inflammatory disease with unknown aetiology. Although clonal expansion of autoreactive T cells has been identified in patients with SS, the clinical correlation of T-cell receptor (TCR) variance in SS remains unclear. Methods: TCRβ repertoire sequencing was performed on 260 SS patients with 3-6 months of follow-up in a cohort study to dynamically assess the characteristics of TCR diversity and their clinical significance. Findings: We found that SS patients had lower TCR diversity, but higher frequency of public clones than healthy controls (HCs). Significant differences were identified in the usage of the variable (V) gene, joining (J) gene, and V-J pairing between SS and HCs. Eighteen SS-associated clones were identified, showing a high sensitivity and specificity for disease classification. TCR diversity was correlated with the presence of dental caries, thrombocytopenia, hepatocholangeitis, antinuclear antibody, anti-SSA/SSB, and hypergammaglobulinemia but not with disease course, number of relapses, arthritis, rheumatoid factor, hypocomplementemia or disease activity defined by SSDAI. During follow-up, the TCR abnormalities remained, represented by more altered V/J usage and higher frequencies of SS-associated clones. Among SS patients, the sensitive subgroup had increased TCR diversity after treatment. Eighty-five SS-sensitivity associated TCRs were identified and used for sensitivity classification by cross validation with high specificity and sensitivity. Interpretation: These results demonstrate that the TCR repertoire could provide insights into the disease status and prognosis in SS and other autoimmune diseases. Funding: This study was funded by the National Key Research and Development Program of China (2016YFC0906201), Sichuan Science and Technology Program (2020YJ0223), and the 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD18015).http://www.sciencedirect.com/science/article/pii/S2352396422004340Sjogren's syndromeT-cell receptorRepertoireClonotype |
| spellingShingle | Chenyang Lu Xuenan Pi Wangdong Xu Pingying Qing Honghu Tang Yanhong Li Yi Zhao Xiao Liu Huairong Tang Yi Liu Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome EBioMedicine Sjogren's syndrome T-cell receptor Repertoire Clonotype |
| title | Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome |
| title_full | Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome |
| title_fullStr | Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome |
| title_full_unstemmed | Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome |
| title_short | Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome |
| title_sort | clinical significance of t cell receptor repertoire in primary sjogren s syndrome |
| topic | Sjogren's syndrome T-cell receptor Repertoire Clonotype |
| url | http://www.sciencedirect.com/science/article/pii/S2352396422004340 |
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