Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: In recent years, several studies have characterized the gene expression signatures of different tissues affected by ANCA-associated vasculitis (AAV). The purpose of this study is to test the hypothesis that there are commonly preserved disease pathways in all AAV tissues thus far characterized.
Methods: Gene expression data were collected from the three AAV tissues thus far characterized (orbit, peripheral leukocytes, and sinus brushings). The set of differentially up and down-regulated genes from each study were analyzed using the Cytoscope software application with the Reactome FI plugin–this is a pathway-based network analysis system using expert curated knowledge of protein-protein interactions. The pathways data were adjusted for multiple comparisons using a multi-dimensional local false discovery rate (md-locfdr), which estimates the probability of a false discovery of a given pathway in all three tissues analyzed.
Results: Four individual genes were upregulated in all three tissues—IL1RN, TLR2, SCL11A1, and MMP9. After multiple comparison adjustments, the network pathway analysis revealed 28 pathways associated with all three tissues. The most strongly associated pathway for all three tissues was the neutrophil degranulation pathway (md-locfdr=1.0×10-12), followed by the osteoclast differentiation (md-locfdr=3.8×10-05), cell surface interactions at the vascular wall (md-locfdr=4.2×10-04), signaling by interleukins (md-locfdr=6.1×10-04), and phagosome (md-locfdr =0.003) pathways. There were no downregulated genes or pathways common to all three tissues.
Conclusion: This analysis identified individual genes and pathways of disease common to all AAV tissues thus far characterized. The use of a network pathway analysis allowed us to identify pathologic mechanisms that were not readily apparent in the commonly expressed genes alone. Many of these pathways are consistent with current theories about infectious drivers and the crossroads of innate and adaptive immune mechanisms. In addition, this analysis highlights novel pathways, such as vessel wall interactions and platelet activation, which require further investigation.
To cite this abstract in AMA style:Friedman M, Choi D, Planck S, Rosenbaum JT, Sibley C. Gene Expression Pathways across Multiple Tissues in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Reveal Core Pathways of Disease Pathology [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/gene-expression-pathways-across-multiple-tissues-in-anti-neutrophil-cytoplasmic-antibody-associated-vasculitis-reveal-core-pathways-of-disease-pathology/. Accessed May 29, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/gene-expression-pathways-across-multiple-tissues-in-anti-neutrophil-cytoplasmic-antibody-associated-vasculitis-reveal-core-pathways-of-disease-pathology/