ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0053

Susceptibility Factors for Psoriatic Arthritis Single-cell RNA-Sequencing of Patients with Psoriatic Disease

Ameth Garrido1, Rohan Machhar2, Omar Cruz Correa3, Darshini Ganatra3, Sarah Crome4, Joan Wither3, Igor Jurisica5 and Dafna Gladman6, 1Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada, 2Krembil Research Institute, University Health Network, Toronto, ON, Canada, 3University Health Network, Toronto, ON, Canada, 4Ajmera Transplant Centre, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada, 5Schroeder Arthritis Institute, Krembil Research Institute, Toronto, ON, Canada, 6Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, Toronto, ON, Canada

Meeting: ACR Convergence 2021

Keywords: , , ,

Session Information

Date: Saturday, November 6, 2021

Title: Spondyloarthritis Including PsA – Basic Science Poster (0046–0068)

Session Type: Poster Session A

Session Time: 8:30AM-10:30AM

Background/Purpose: Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease that affects 30% of patients with psoriasis. Thus, early diagnosis of this subgroup is crucial to reduce disease progression and prevent joint destruction. GWAS and epigenome studies have identified major susceptibility genes albeit having low odds ratios. Single cell RNA-seq provides increased resolution to identify novel cell types and cell-specific differential gene expression. We aim to identify a set of genes that can lead to an earlier diagnosis of PsA.

Methods: Three PsA patients, three cutaneous psoriasis (PsC) patients and two healthy control samples were profiled with 10X genomics single cell RNA-seq. The patients recruited were recently diagnosed with PsA and were not treated with biologics. The gene profiles of peripheral blood mononuclear cells (PBMC) were selected for sequencing. The raw data were processed using the CELLRANGER pipeline. R version 4.0.1 was used for secondary analysis using the following packages: SingleCellExperiment, scran, scater and Seurat. These packages were used to cluster the cells and perform differential gene expression analysis. Cell clusters were manually annotated based on canonical markers generated from the ‘findallmarkers’ function in Seurat and differentially expressed genes were selected in each cluster. A ranking was assigned to genes in each cluster to identify suitable targets for validation by considering the results of the differential gene expression analysis, network analysis using the Integrated Interactions Database version 2018-11, GO and pathway over-representation analysis which was conducted using Pathdip 4.0. A score was assigned to every gene based on their log fold change difference, adjusted p-value in the differential gene expression analysis, closeness centrality and connectivity in the protein interaction network.

Results: The aggregated data revealed the presence of 18 clusters with 15 unique cell types. In the T-Cell and Classical Monocyte populations pathways related to inflammation, cell migration and apoptosis were enriched. Genes belonging to the AP-1 transcription factor JUN, JUNB, and FOS were ranked highly across both T-Cell and Monocyte clusters. Interestingly, the classical monocyte population included several highly ranked genes that are responsive to interferon-alpha: MNDA and IFI6. The genes that are listed above were found to be consistently differentially expressed across healthy controls and either PSA or PsC.

Conclusion: Several genes were identified in specific cell types; these will be validated using multiple gene and protein assays.

Disclosures: A. Garrido, None; R. Machhar, None; O. Cruz Correa, None; D. Ganatra, None; S. Crome, None; J. Wither, None; I. Jurisica, None; D. Gladman, AbbVie, 2, 5, Amgen, 2, 5, Eli Lilly, 2, 5, Galapagos, 2, 5, Gilead, 2, 5, Janssen, 2, 5, Novartis, 2, 5, Pfizer, 2, 5, UCB, 2, 5, Celgene, 2, 5, Bristol Myers Squibb, 2, 5.

To cite this abstract in AMA style:

Garrido A, Machhar R, Cruz Correa O, Ganatra D, Crome S, Wither J, Jurisica I, Gladman D. Susceptibility Factors for Psoriatic Arthritis Single-cell RNA-Sequencing of Patients with Psoriatic Disease [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/susceptibility-factors-for-psoriatic-arthritis-single-cell-rna-sequencing-of-patients-with-psoriatic-disease/. Accessed .

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/susceptibility-factors-for-psoriatic-arthritis-single-cell-rna-sequencing-of-patients-with-psoriatic-disease/