Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome

Chenyang Lu; Xuenan Pi; Wangdong Xu; Pingying Qing; Honghu Tang; Yanhong Li; Yi Zhao; Xiao Liu; Huairong Tang; Yi Liu

doi:10.1016/j.ebiom.2022.104252

Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome

EBioMedicine. 2022 Oct:84:104252. doi: 10.1016/j.ebiom.2022.104252. Epub 2022 Sep 9.

Authors

Chenyang Lu¹, Xuenan Pi², Wangdong Xu³, Pingying Qing⁴, Honghu Tang⁴, Yanhong Li¹, Yi Zhao⁴, Xiao Liu⁵, Huairong Tang⁶, Yi Liu⁷

Affiliations

¹ 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.
² National Frontier Center of Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
³ Department of Evidence-Based Medicine, Southwest Medical University, Luzhou, China.
⁴ Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China.
⁵ BGI-Shenzhen, Shenzhen 518083, China; Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
⁶ Health Management Center, West China Hospital of Sichuan University, Chengdu 610041, China. Electronic address: 1651682099@qq.com.
⁷ 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. Electronic address: yi2006liu@163.com.

Abstract

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).

Keywords: Clonotype; Repertoire; Sjogren's syndrome; T-cell receptor.

MeSH terms

Antibodies, Antinuclear
Cohort Studies
Dental Caries*
Humans
Receptors, Antigen, T-Cell / genetics
Sjogren's Syndrome* / etiology
Sjogren's Syndrome* / genetics

Substances

Antibodies, Antinuclear
Receptors, Antigen, T-Cell