Spatial profiling of giant cell arteritis tissues reveals immune heterogeneity and potential predictors of glucocorticoid response
Year: 2025
Type: article
Study design: Observational Study
Abstract: OBJECTIVES: Giant cell arteritis (GCA) is an immune-mediated vasculitis of large- and medium-sized arteries that can lead to systemic symptoms and irreversible vision loss. Glucocorticoids (GCs) remain the primary treatment but fail to induce sustained remission (SR) in approximately half of patients, resulting in disease relapses and significant treatment-related toxicity. We aimed to identify tissue-based markers at disease onset capable of distinguishing patients who later achieve SR from those who do not (non-remission [NR]) under GC monotherapy. METHODS: Using spatial biology techniques, we performed a comprehensive analysis of GCA-affected arterial tissues obtained at disease onset, correlating molecular profiles with clinical trajectory. We compared gene expression and immune cell populations between SR and NR groups, corroborated key findings by immunohistochemistry, and evaluated the diagnostic performance of identified biomarkers. RESULTS: Patients with NR exhibited an upregulation of extracellular matrix remodelling (ECM) and T cell activation pathways, reflecting persistent inflammation and fibrotic-like responses. By contrast, SR cases were distinguished by an enrichment of immunoglobulin G-producing plasma cells in the adventitia, which correlated with increased macrophage infiltration in the intima. Quantitative analyses suggested that combining plasma cell and macrophage markers could accurately predict GC responsiveness. CONCLUSIONS: Our findings reveal an immunopathologic signature in GCA at diagnosis, characterised by plasma cell-rich infiltrates associated with favourable outcomes, and ECM- and T cell-associated inflammation enriched in GC-refractory cases. These insights could foster a precision medicine approach to GCA management, enabling patient stratification for GC-sparing therapies and optimising patient outcomes.
Source: Annals of the Rheumatic Diseases
Authors: Cecilia Ansalone, Samuel McAllister, Ethan S. Pickerill, Lin Zhang, David C. Gemperline, Annie Peacock, Ishita Gupta, Dominic Mcgovern, Victoria Kellior, Evelyn Qian, Aysin Tulunay Virlan, Maria Laura Vieri, Holly Leslie, Yoana Doncheva, Claire Kennedy Dietrich, Sylvia Wright, Paul Cauchi, Timothy Beckman, Lisa Hutton, John Cole, Nigel B. Jamieson, Isabella H. Wulur, Ajay Nirula, Iain B. McInnes, Robert J. Benschop, Carl S. Goodyear, Neil Basu
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,870
Funder: Eli Lilly and Company
OpenAlex ID: W4415314240