Background/Purpose: Background: Giant cell arteritis (GCA) is an inflammatory vasculitis of medium and large arteries with a spectrum of phenotypes. Cranial-GCA is associated with blindness and positive temporal artery (TA) biopsies, while large-vessel GCA more often presents with PMR and aortic complications. The basis for differing vessel involvement is unknown. Histopathology shows T-cell-dominant infiltrates in TAs, while more B-cells and developed artery tertiary lymphoid organs (ATLOs) are found in aortas. We hypothesize that gene expression differences, particularly in pathways of cell recruitment and adhesion, may underlie these patterns.

Methods: Methods: Three transcriptome analyses were completed: (1) TA biopsies from biopsy-positive GCA (n=21) versus controls (n=30), RNAseq; (2) aortic tissue from GCA (n=19) versus atherosclerotic controls (n=19), RNAseq (GSE224526); (3) pulmonary vascular bed biopsy in another disease with classic granulomatous inflammation, sarcoid (n=6) versus controls (n=6) , microarray (GSE16538). Differential expression (DE) was assessed with DESeq2 or GEO2R. Pathways of chemokines, cell adhesion molecules (CAM), and fibrosis-related genes (FRG) were obtained from Reactome and FibROAD.

Results: Results: DE genes included 2,261 in GCA-TA, 9,078 in GCA-aorta, and 1,142 in sarcoid. The 135 genes shared across all most likely reflect non-specific granulomatous inflammation. Genes (1,777) significant in both GCA-TA and GCA-aorta but not sarcoid included 35 CAM, 9 chemokines, and 48 FRG. TA-specific genes (342) included 5 CAM, 4 chemokines, and 13 FRG; CCL22 was most upregulated (log2FC4.0) of these chemokines and is known to recruit activated t-lymphocytes, a hallmark of TA lesions. Pathway enrichment analysis found cell adhesion and chemotaxis processes in four of top ten categories (Figure 1). Aorta-specific genes (6,714) included 40 CAM, 13 chemokines, and 85 FRG; CXCL13 was most upregulated (log2FC4.4),and has been reported elevated in circulating B cells in GCA-PMR. CXCL13 may be an integral agent in ALTOs in aortic lesions.

Conclusion: Conclusions: This integrated transcriptome-wide analysis in TA and aortic tissues in GCA highlights vessel-specific chemotaxis, advancing understanding of vascular involvement and informing biomarker and therapeutic development.

Figure 1. Pathway enrichment (biological process) analysis from 342 genes significantly differentially expressed only in temporal artery tissue in GCA vs control. Four of these top 10 belong to chemotaxis and cell adhesion.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/transcriptome-analysis-of-temporal-artery-and-aortic-lesions-highlights-vessel-specific-chemotaxis-and-cell-adhesion-in-gca/