Session Type: Poster Session A
Session Time: 8:30AM-10:30AM
Background/Purpose: CD8+ and CD4+ T cell subsets have been implicated in the pathogenesis of psoriatic disease. Here, we explore the T-cell repertoire in psoriatic disease using single-cell RNA sequencing to identify novel susceptibility markers of disease by focusing on T cells with clonal expansion.
Methods: We profiled frozen peripheral blood mononuclear cells derived from 3 psoriasis, 3 psoriatic arthritis (biologic naïve, matched for age, gender and disease duration) and 2 healthy control samples using 10X genomics 5’ single cell gene expression technology. TCR immune cell profiling was employed, and sequencing data was processed using the CELLRANGER pipeline. We identified 4579 TCRs in psoriasis, 3323 in psoriatic arthritis, and 1843 in healthy control samples. Secondary analysis of TCR beta and alpha chains was conducted in R version 4.0.1 using scran, scater, SingleCellExperiment, Seurat, scREPERTOIRE and Immunarch. The online tool GLIPH2.0 was used to cluster the TCR beta CDR3 amino acid sequences based on motif similarity and VDJdb was used to predict antigen specificity. VDJ gene differential expression analysis was conducted across multiple groups using the Dunn.test function in R.
Results: The shared motifs from the clustering results from GLIPH2.0 comprising only psoriatic arthritis and/or psoriasis patients had a predicted antigen specificity for Cytomegalovirus (CMV) proteins Immediate-Early1 (IE1) or pp65. The variable beta chain genes TRBV2 (FC= 0.14, p-value= 0.033), TRBV7-2(FC=1.49, p-value= 0.0098), TRBV7-7(FC=1.00, p-value= 0.018) and TRBV6-3 (FC= 1.17, p-value=0.033) were elevated and significantly differentially expressed in psoriatic arthritis patients when compared to psoriasis patients. A clonal expansion of CD8+ cytotoxic T-cells was observed in a psoriatic arthritis patient. It accounted for approximately 7% of all clonotypes for that individual. The predicted antigen was IE1 from CMV.
Conclusion: Antigen selection may be occurring in psoriatic arthritis patients. Further investigation is required to determine if the predicted antigens pp65 and IE1 are relevant in the pathogenesis of psoriatic arthritis.
To cite this abstract in AMA style:Garrido A, Machhar R, Cruz Correa O, Crome S, Wither J, Jurisica I, Gladman D. TCR Immune Profiling of Patients with Psoriatic Disease [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/tcr-immune-profiling-of-patients-with-psoriatic-disease/. Accessed January 30, 2023.
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