26rhk03610.3205/26rhk036urn:nbn:de:0183-26rhk0365Meeting AbstractTargeting the vascular adhesion protein-1/Siglec-9 axis in giant cell arteritisGheitasiGheitasiRezaRUniversität Bonn, Uniklinikum Bonn, Medizinische Klinik und Poliklinik III Innere Medizin mit den Schwerpunkten Onkologie, Hämatologie und Rheumatologie, Bonn, DeutschlandauthorPetzinnaPetzinnaSimon M.SMUniversität Bonn, Uniklinikum Bonn, Medizinische Klinik und Poliklinik III Innere Medizin mit den Schwerpunkten Onkologie, Hämatologie und Rheumatologie, Bonn, DeutschlandauthorBauerBauerClaus-JürgenCJUniversität Bonn, Uniklinikum Bonn, Medizinische Klinik und Poliklinik III Innere Medizin mit den Schwerpunkten Onkologie, Hämatologie und Rheumatologie, Bonn, DeutschlandauthorZahmatkeshZahmatkeshMozhganMUniversität Bonn, Uniklinikum Bonn, Medizinische Klinik und Poliklinik III Innere Medizin mit den Schwerpunkten Onkologie, Hämatologie und Rheumatologie, Bonn, DeutschlandauthorUssemUssemLeticiaLUniversity of Bonn, University Hospital Bonn, Department of Ophthalmology, Division of Ophthalmic Pathology, Bonn, DeutschlandauthorHerwig-CarlHerwig-CarlMartinaMUniversity of Bonn, University Hospital Bonn, Department of Ophthalmology, Division of Ophthalmic Pathology, Bonn, DeutschlandauthorSchäferSchäferValentin SebastianVSUniversität Bonn, Uniklinikum Bonn, Medizinische Klinik und Poliklinik III Innere Medizin mit den Schwerpunkten Onkologie, Hämatologie und Rheumatologie, Bonn, DeutschlandauthorGerman Medical Science GMS Publishing House
Düsseldorf
61020260909englThis is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License.Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung).M0656036Deutsche Gesellschaft für RheumatologieDeutsche Gesellschaft für Orthopädische RheumatologieGesellschaft für Kinder- und Jugendrheumatologie54. Kongress der Deutschen Gesellschaft für Rheumatologie und Klinische Immunologie (DGRh), 36. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR), 40. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)Deutscher Rheumatologiekongress 2026Experimentelle & Translationale RheumatologieLeipzig2026090920260912ET.10TextIntroduction: The precise pathogenic mechanisms facilitating localized vascular inflammation in giant cell arteritis (GCA) remains incompletely understood. Vascular Adhesion Protein-1 (VAP-1) and its leukocyte ligand, Sialic Acid Binding Ig-like Lectin 9 (Siglec-9), govern critical steps in leukocyte extravasation. This study aimed to characterize the VAP-1/Siglec-9 axis in GCA and evaluate the diagnostic feasibility of [68Ga] Ga-DOTA-Siglec-9 positron emission tomography computed tomography (PET/CT) for detecting active vasculitis.Methods: A prospective cohort of patients with GCA and age- and sex-matched healthy control subjects was recruited at the Division of Rheumatology, University Hospital Bonn. Tissue expression of VAP-1 was assessed via immunohistochemistry in temporal artery biopsies (TABs). Soluble VAP-1 (sVAP-1) and Matrix Metalloproteinases (MMPs) were quantified in serum via Enzyme-linked Immunosorbent Assay. Peripheral blood mononuclear cells (PBMCs) were analyzed utilizing flow cytometry to determine Siglec-9 surface expression and bulk RNA-sequencing to define transcriptomic signatures. Molecular imaging was performed in a subset of active GCA patients using [68Ga] Ga-DOTA-Siglec-9 PET/CT, with follow-up scans acquired two hours post-glucocorticoid administration. Furthermore, a cohort of GCA patients in stable remission was subjected to transcriptomic profiling.Results: Histopathological analysis revealed marked VAP-1 expression localized (in addition to the staining reaction in the vascular smooth muscle cells) specifically to the hyperplastic neointima of inflamed GCA arteries (Figure 1A-C ). Conversely, circulating sVAP-1 (Figure 1D ) and its shedding enzymes MMP-2 (Figure 1E ) and MMP-9 (Figure 1G ) were decreased, whereas pro-inflammatory MMP-3 (Figure 1F ) was elevated in active GCA patients. Flow cytometry demonstrated significant upregulation of Siglec-9 on classical and non-classical monocytes, plasmablasts, plasma cells, and natural killer cells (Figure 1H ). Bulk RNA-sequencing revealed a profound proinflammatory signature, extensive myeloid skewing, and a deficit in regulatory T cells (Figure 1J ). An in vivo, [68Ga] Ga-DOTA-Siglec-9 PET/CT exhibited a localized tracer uptake in the thoracic and abdominal aorta and axillary arteries (not shown). Transcriptomic analysis of patients in stable remission identified a distinct molecular signature driven by dysregulated cell adhesion and wound-healing networks, rather than a return to homeostatic baseline.Conclusion: The VAP-1/Siglec-9 axis is highly dysregulated in active GCA, bridging localized endothelial activation with systemic myeloid expansion. [68Ga] Ga-DOTA-Siglec-9 PET/CT serves as a sensitive, dynamically responsive molecular imaging modality for VAP-1 mediated vascular inflammation. Furthermore, stable disease remission is characterized by persistent transcriptional alterations in cell adhesion pathways, highlighting an incomplete restoration of immune homeostasis.Petzinna SMKüppers JSchemmer BKernder ALBauer CJvon der Emde LSalam BDistler JHWWinklbauer AEssler MSchäfer VSCase report: Detecting giant cell arteritis in2024Front Immunol1501790Petzinna SM, Küppers J, Schemmer B, Kernder AL, Bauer CJ, von der Emde L, Salam B, Distler JHW, Winklbauer A, Essler M, Schäfer VS. Case report: Detecting giant cell arteritis in [68Ga]Ga-DOTA-Siglec-9-PET/CT. Front Immunol. 2024 Dec 16;15:1501790. DOI: 10.3389/fimmu.2024.1501790http://dx.doi.org/10.3389/fimmu.2024.1501790011
Figure 1: Dysregulation of the VAP-1/Siglec-9 Axis and systemic immune remodeling in active giant cell arteritis. (A–C) Representative micrographs of temporal artery biopsies. (A) Hematoxylin and Eosin (H&E) staining of active GCA. (B, C) Immunohistochemical staining for VAP-1 in an inflamed artery demonstrating intense expression. (D) Soluble VAP-1 (sVAP-1), (E) Matrix metalloproteinase-2 (MMP-2), (F) Matrix metalloproteinase-3 (MMP-3), and (G) Matrix metalloproteinase-9 (MMP-9) concentrations (1). (H) Flow cytometric quantification of Siglec-9 positive cells (%) across distinct PBMCs subsets in active disease (orange) compared to controls (gray). (J) Stacked bar plots illustrating deconvolutions of relative frequencies of circulating immune cell populations in newly diagnosed patients compared to controls.