Using T-Cell Receptor Diversity as a Diagnostic Marker for SLE and RA

Chimeric antigen receptor (CAR) on T-cell, illustration. The CAR structures are blue, with the cutaway foreground showing one spanning the cell membrane. These CARs are on the surface of an engineered T-cell. CARs are engineered cell receptors that allow T cells to recognize and attack cancer cells in a specific way. They are built by connecting several functional parts from different proteins. This receptor has a signal protein (ZAP70, purple, lower right) attached to the intracellular domain (bottom).
Researchers used peripheral blood samples from patients with systemic lupus erythematosus and rheumatoid arthritis and a group of healthy participants to identify novel biomarkers to accurately diagnose and monitor SLE and RA.

Characteristics of T-cell receptor (TCR) diversity can potentially provide novel insights into patient disease status and possible therapeutic agents, according to research published in the Annals of the Rheumatic Diseases.

Although TCR diversity determines autoimmune responses in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), the characteristics of variations in TCR diversity — and the associated clinical significance — is unknown.

Researchers used peripheral blood samples from patients with SLE (n = 877) and RA (n = 206) and a group of healthy control participants (n = 439) to identify novel biomarkers for the accurate diagnosis and monitoring of both SLE and RA.

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In total, investigators identified 7.5 million, 2.7 million, and 8.1 million unique TCR clones in patients with SLE and RA and healthy control participants, respectively. The researchers found that patients in the SLE and RA groups both showed decreased Shannon entropy, with the smallest values in the SLE group. Accumulative frequencies for the top 100 or 50 TCR clones in patients with SLE or RA were significantly higher than in healthy control participants.

Researchers noted significant differences in the variable, joining, and variable-joining pairing between SLE or RA and healthy control groups. According to investigators, these differences can be used to discriminate the groups “with perfect accuracy.” In total, they identified 198 SLE-associated and 53 RA-associated TCR clones that were used for disease classification with high specificity and sensitivity. Clones associated with either condition had common features and a high similarity for both autoimmune diseases, although SLE displayed a higher heterogeneity of TCRs than RA.

“The interplay between autoimmunity and infections has been discussed for many years but remains elusive,” the researchers wrote. “Our discovery of the enrichment of pathogen specific T cells in autoimmune diseases is in line with clinical observations and supplements the evidence from a brand new perspective.”

They continued that “given the sharing of associated T cells in both SLE and RA, it is not surprising TCRs targeting other autoimmune related phenotypes, such as [multiple sclerosis] or allergy, are more prevalent in SLE.”

The researchers concluded that this “large-scale work moves a step forward in demonstrating the clinical utility of TCR repertoire sequencing to assist diagnosis, treatments and potentially early [detection] of autoimmune diseases.”


Liu X, Zhang W, Zhao M, et al. T cell receptor β repertoires as novel diagnostic markers for systemic lupus erythematosus and rheumatoid arthritis [published online May 17, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-215442