POS0094 INSIGHT INTO GIANT CELL ARTERITIS PATHOGENESIS BY NANOSTRING NCOUNTER GENE EXPRESSION PROFILING IN TEMPORAL ARTERY BIOPSIES

Background Giant Cell Arteritis (GCA) is a systemic inflammatory disease that affects large and medium-sized arteries. It the most common vasculitis in people older than 50 years of age [1]. Temporal artery biopsies (TABs) are routinely performed for diagnosis, giving invaluable opportunity to analyze inflamed tissues. Different histological patterns inflammation can be found TABs: transmural (TMI) frequent pattern (78% positive TABs), while limited adventitia (ILA) 7% TABs [2]. not known if ILA precedes TMI or they distinct GCA subsets. Knowledge on pathogenesis growing [3], but high-throughput assays still scarce [4-7]. patients actually treated with glucocorticoids, irrespective clinical presentations patterns. necessary increase knowledge molecular features implement precision medicine. Objectives To identify differentially expressed genes (DEGs) TAB from versus controls. GCA. Methods A retrospective cohort subjected at AUSL-IRCCS Reggio Emilia (Italy) was included: 42 had TMI; 7 ILA; normal received different diagnosis. All were naïve therapy 4/7 receiving glucocorticoids time TABs. RNA extracted formalin-fixed paraffin-embedded The expression 770 profiled NanoString nCounter PanCancer Immune Profiling Panel. Data analyzed nSolver software 4.0. thresholding using negative control probes applied, then data normalized over 18 housekeeper genes. DEGs fold changes >2.0 Benjamini-Yekutieli adjusted p-values <0.05 considered significant. Unsupervised clustering nSolver. Pathway analysis DAVID. Results based revealed two groups samples: first group contained all plus ILA, second 41/42 TMI. In particular, TNF superfamily related senescence allowed cluster showed 31 down- 268 up-regulated compared TABs; 20 135 ILA. gene profile similar 47 reached >2.0, did maintain statistical significance after correction multiple testing. These also modulated chemokine CCL18 top gene, cell adhesion molecule MCAM down-regulated CD86 costimulatory molecule, marker antigen-presenting cells, detected only JAK3 resulted increased TMI, JAK1 JAK2 modulated. CD27 activating immune checkpoint 6/7 it following pathways enriched DEGs: TLR signaling, antigen processing presentation via MHC class II, regulation T activation, cellular responses IL-1, TNF, IFNγ. Conclusion transcriptome set deregulated both TABs, indicating might represent early stages disease. Gene profiling deepen pathogenesis. References [1]Salvarani C. Nat Rev Rheumatol 2012 [2]Cavazza A. Am J Surg Pathol 2014 [3]Ciccia F. Lancet 2021 [4]Andrew N. Neurol Neuroimmunol Neuroinflamm [5]Patrick Ann Rheum Dis 2016 [6]Friedman M. Arthritis 2022, ACR abstract 0486 [7]Croci S. Acknowledgements Azienda Unità Sanitaria Locale (AUSL)-IRCCS, Emilia, Italy: “Bando per la valorizzazione della Ricerca Istituzionale 2019” Foundation Research Rheumatology (FOREUM). Disclosure Interests None Declared.