Objective T cell receptor (TCR) diversity determines the autoimmune responses in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is closely associated with autoimmune diseases prognosis and prevention. However, the characteristics of variations in TCR diversity and their clinical significance is still unknown. Large series of patients must be studied in order to elucidate the effects of these variations.
Methods Peripheral blood from 877 SLE patients, 206 RA patients and 439 healthy controls (HC) were amplified for the TCR repertoire and sequenced using a high-throughput sequencer. We have developed a statistical model to identify disease-associated TCR clones and diagnose autoimmune diseases.
Results Significant differences were identified in variable (V), joining (J) and V-J pairing between the SLE or RA and HC groups. These differences can be utilised to discriminate the three groups with perfect accuracy (V: area under receiver operating curve > 0.99). One hundred ninety-eight SLE-associated and 53 RA-associated TCRs were identified and used for diseases classification by cross validation with high specificity and sensitivity. Disease-associated clones showed common features and high similarity between both autoimmune diseases. SLE displayed higher TCR heterogeneity than RA with several organ specific properties. Furthermore, the association between clonal expansion and the concentration of disease-associated clones with disease severity were identified, and pathogen-related TCRs were enriched in both diseases.
Conclusions These characteristics of the TCR repertoire, particularly the disease-associated clones, can potentially serve as biomarkers and provide novel insights for disease status and therapeutical targets in autoimmune diseases.
- autoimmune diseases
- systemic lupus erythematosus
- rheumatoid arthritis
- t cells
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XL, WZ and MZ contributed equally.
Handling editor Prof Josef S Smolen
Correction notice This article has been corrected since it published Online First. The fourth author's name has been corrected.
Contributors QL, XL, WZ and MZ designed the study, analysed the data and wrote the manuscript. LF, JW, LW, LL, SW, LL, XW, TL, YZ, ZW, MF and HP performed TCR sequencing and data analysis. LL, SL, ZW, YL, YY, JJ, YT, BZ, XG, CH, QL, XL, JC, FL, GL, HZ, HL, ZX JL, YL, HY, HL and HW collected the samples and information of patients and healthy subjects. QL, XL, HY and JW supervised the study.
Funding This study was supported by the National Key Research and Development Program of China (2016YFC0903900), the National Natural Science Foundation of China (No. 81430074, No.81522038 and No. 81220108017), the Key research and development plan of Hunan Province (2017SK2042) and the Shenzhen Municipal Government of China (No. JCYJ20170817145536203 and JCYJ20170817145428361).
Competing interests None declared.
Patient consent for publication Obtained.
Ethics approval The study has been approved by the ethical committee of the Second Xiangya Hospital of Central South University.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement The study data have been made publicly available at pan immune repertoire database (PIRD, https://db.cngb.org/pird/),22 which is located in China National GeneBank (CNGB). The project ID in PIRD are P18081001, P18081101 and P18080801.
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