Background/Purpose:

T cell receptors (TCRs) are a vital component of the adaptive immune system and TCR repertoire diversity is considered a measure of the immune system’s strength and competency. T cells have been implicated in the progression of systemic sclerosis (SSc), yet the TCR repertoire in SSc remains understudied. Here, we present findings from TCR sequencing in SSc patients to characterize their TCR repertoire.

Methods:

Peripheral blood mononuclear cells (PBMCs) were collected from 11 patients with SSc and 7 controls, matched for age, gender, and race. We performed TCR sequencing on genomic DNA isolated from CD14- lymphocytes. RNA-seq was also performed on RNA isolated from these cell populations. We used various metrics including CHAO1, Shannon Index, and Inverse-Simpson to quantify diversity of the TCR repertoire in each sample. Pearson correlation and Wilcoxon Rank Sum Test were used to relate clinical covariates to TCR repertoire diversity in SSc patients and controls. We used edgeR (Bonferroni-Holmes corrected p<0.05) to identify differentially expressed genes from RNA-seq data and identified significantly enriched Gene Ontology biological pathways using g:Profiler (g:SCS corrected p <0.05).

Results:

We quantified measures of TCR repertoire diversity for each individual sample and correlated these measures with clinical variables. Reduced TCR repertoire diversity was associated with increased age in both SSc and controls, as previously reported (R=-0.44, p=0.06). There was a statistically significant reduction in TCR diversity in SSc patients compared to controls (p=0.0154). Reduction in TCR diversity was most notable for patients with limited cutaneous SSc, though this did not reach statistical significance in our small sample size. There were no statistically significant relationships between TCR repertoire diversity and FVC, DLCO, or disease duration. We identified a total of 5735 differentially expressed genes (2651 up-regulated, 3084 down-regulated) in SSc samples compared to healthy control samples. Upregulated biological processes for SSc lymphocytes included CD4+, alpha beta activation, Type I interferon production, T cell differentiation, mRNA processing, and cell cycle(p<0.05). Upregulated biological processes for control samples included leukocyte degranulation, lipid oxidation, and translational termination.

Conclusion:

We find a reduced diversity of TCR repertoire in patients with SSc relative to healthy controls. Gene expression analyses indicate that circulating T cells of SSc patients may be different from healthy controls, favoring suppression of effector Th1 generation, consistent with the development of autoimmunity.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterizing-the-t-cell-receptor-repertoire-in-patients-with-systemic-sclerosis/