Xiao Liu 1,2 , Wei Zhang 1,2 , Ming Zhao 3 , Longfei Fu 1,2 , Limin Liu 3 , Jinghua Wu 1,2 , Shuangyan Luo 3 , Longlong Wang 1,2 , Zijun Wang 3 , Liya Lin 1,2 , Yan Liu 3 , Shiyu Wang 1,2 , Yang Yang 3 , Lihua Luo 1,2 , Juqing Jiang 3 , Xie Wang 1,2 , Yixin Tan 3 , Tao Li 1,2 , Bochen Zhu 3 , Yi Zhao 1,2 , Xiaofei Gao 3 , Ziyun Wan 1,2 , Cancan Huang 3 , Mingyan Fang 1,2 , Qianwen Li 3 , Huanhuan Peng 1,2 , Xiangping Liao 4 , Jinwei Chen 5 , Fen Li 5 , Guanghui Ling 5 , Hongjun Zhao 6 , Hui Luo 6 , Zhongyuan Xiang 7 , Jieyue Liao 3 , Yu Liu 3 , Heng Yin 3 , Hai Long 3 , Haijing Wu 3 , Huanming Yang 1,2,8 , Jian Wang 1,2,8 , Qianjin Lu 9 Show Affiliations »
Abstract
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. © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
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 . © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Entities: Disease
Species
Keywords:
autoimmune diseases; rheumatoid arthritis; systemic lupus erythematosus; t cells
Mesh： See more »
Substances： See more »
Year: 2019
PMID： 31101603 DOI： 10.1136/annrheumdis-2019-215442
Source DB: PubMed Journal: Ann Rheum Dis ISSN： 0003-4967 Impact factor: 19.103