T cell receptor β repertoires as novel diagnostic markers for systemic lupus erythematosus and rheumatoid arthritis

Abstract

ObjectiveT 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.MethodsPeripheral 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.ResultsSignificant 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.ConclusionsThese 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.

Peptide-Based Vaccination Therapy for Rheumatic Diseases

“…However, the molecular mechanisms underlying the therapeutic roles of TCR peptide-based vaccines are still not clearly defined and further studies are needed on this aspect. The advances in the technologies to assess TCR repertoire have provided much help in precisely identifying dominant TCR repertoire involving the development of rheumatic diseases, which may further facilitate the development of TCR peptidebased therapeutic vaccines for those diseases [100,101].…”

Meeting Report of the 4th Annual Meeting of the Chinese Society for Investigative Dermatology: Reflections on the Rise of Cutaneous Biology Research in China

“…The 5th Annual Meeting of the Chinese Society for Investigative Dermatology will take place in Xi'an on September 11e13, 2020. Cai et al, 2011;Jin and Wang, 2014;Qiao et al, 2019;Sun et al, 2010;Wu et al, 2018;Yang et al, 2017;Zhang et al, 2013cZhang et al, , 2009bZhou et al, 2016;Zuo et al, 2015 Systemic lupus erythematosus Han et al, 2009;Liu et al, 2019;Morris et al, 2016;Wen et al, 2018;Zhao et al, 2018Zhao et al, , 2016 Vitiligo Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC. Impaired activation of the Nrf2-ARE signaling pathway undermines H 2 O 2 -induced oxidative stress.…”

Understanding and measuring human B‐cell tolerance and its breakdown in autoimmune disease

“…148,149 Intriguingly, specific TCR repertoire profiles have been associated with SLE or other autoimmune diseases and may have the potential to differentiate between these conditions. 150 These observations need to be formally validated and the ability of BCR profiles to differentiate SLE from other autoimmune diseases, remains to be investigated.…”