Use of High-plex Data Reveals Novel Insights into the Temporal Artery Processus of Giant Cell Arteritis

Simon Parreau¹, Elsa Molina², Stéphanie Dumonteil¹, Radjiv Goulabchand³, Thomas Naves⁴, Melanie Bois⁵, Anne-Laure Fauchais¹, Eric Liozon⁶, Marie-Odile Jauberteau⁴, Cornelia M. Weyand⁷ and Kim-Heang Ly¹, ¹Dupuytren Hospital, Limoges, France, ²Next Generation Sequencing Core, Salk Institute for Biological Studies, La Jolla, CA, ³University of California San Diego, La Jolla, CA, ⁴INSERM U1308, Limoges, France, ⁵Mayo Clinic, Rochester, MN, ⁶Department of Internal Medicine, University Hospital of Limoges, Limoges Cedex, Limoges, France, ⁷Mayo Clinic School of Medicine and Stanford University, Rochester, MN

Meeting: ACR Convergence 2023

Keywords: genomics, giant cell arteritis

Session Information

Date: Sunday, November 12, 2023

Title: (0013–0039.5) Genetics, Genomics & Proteomics Poster

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Uncover the key coding genes to define new biomarkers or pathways associated with GCA by performing the first in situ spatial profiling characterization of molecular actors involved in temporal arteries from GCA patients in comparison to normal arteries.

Methods: From human formalin-fixed paraffin-embedded temporal artery biopsy samples (GCA n=9; controls n=7), we performed a whole transcriptome analysis by using NanoString GeoMx Digital Spatial Profiler (DSP) (2). A total of 59 individual regions of interest (ROIs) were created within each of the 4 layers for each individual artery. After ROIs collection and library construction, samples were sequenced on the Illumina NovaSeq 6000 platform and reads were digitally quantified and normalized using GeoMx DSP Data Analysis software. Differential expressed genes (DEGs) (fold change >2 or < -2, p-adjusted < 0.05) were compared for each layer, to build a spatial and pharmacogenomic network in disease course.

Results: Overall, we found that most of the transcriptome studied (12076 genes) was upregulated in GCA arteries. Precisely, 350, 340, 142 and 5 DEGs were found in intima, media, adventitia, and perivascular tissue respectively. Enrichment analysis highlighted that inflammation/immune-related functions and vascular remodeling were significantly limited to intima and media layers. Upregulated immune-related functions concerned macrophage differentiation & T cell, B cell, complement activations. Regarding vascular remodeling pathways, we found an upregulation of: (i) collagen metabolic process and fibroblast proliferation concerning the 3 artery layers, (ii) angiogenesis & epithelial cell migration in intima and media layers, (iii) smooth muscle cell proliferation & ossification in intima layer. Our pharmacogenomic network analysis identified genes that could potentially be targeted by immunosuppressive drugs currently approved or new immunotherapies.

Conclusion: Our findings provide the first in situ spatial profiling characterization of molecular actors involved in GCA which is essential for the discovery of potential new therapeutic targets to cure this disease. The differential spatial upregulation of genes involved in inflammatory process and vascular remodeling suggests a differential chronological involvement of each layer of the artery.

Disclosures: S. Parreau: NanoString Technologies Inc., Seattle, WA, 5; E. Molina: NanoString Technologies Inc., Seattle, WA, 5; S. Dumonteil: None; R. Goulabchand: None; T. Naves: None; M. Bois: None; A. Fauchais: None; E. Liozon: None; M. Jauberteau: None; C. Weyand: None; K. Ly: None.

To cite this abstract in AMA style:

Parreau S, Molina E, Dumonteil S, Goulabchand R, Naves T, Bois M, Fauchais A, Liozon E, Jauberteau M, Weyand C, Ly K. Use of High-plex Data Reveals Novel Insights into the Temporal Artery Processus of Giant Cell Arteritis [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/use-of-high-plex-data-reveals-novel-insights-into-the-temporal-artery-processus-of-giant-cell-arteritis/. Accessed .

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