Proteomic Profiling of the Large-Vessel Vasculitis Spectrum Identifying Shared Signatures of Innate Immune Activation and Stromal Remodeling.
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All Authors
Maughan, RT.
Macdonald-Dunlop, E.
Haroon-Rashid, L.
Sorensen, L.
Chaddock, N.
Masters, S.
Porter, A.
Peverelli, M.
Pericleous, C.
Hutchings, A.
LTHT Author
Sorensen, Louise
Morgan, Ann-Wendy
Morgan, Ann-Wendy
LTHT Department
NIHR Leeds Biomedical Research Centre
Rheumatology
Rheumatology
Non Medic
Publication Date
2025
Item Type
Journal Article
Language
Subject
Subject Headings
Abstract
OBJECTIVE: Takayasu arteritis (TAK) and giant cell arteritis (GCA), the most common forms of large-vessel vasculitis (LVV), can result in serious morbidity. Understanding the molecular basis of LVV should aid in developing better biomarkers and treatments.
METHODS: Plasma proteomic profiling of 184 proteins was performed in two cohorts. Cohort 1 included patients with established TAK (n = 96) and large-vessel GCA (LV-GCA) (n = 35) in addition to healthy control participants (HCs) (n = 35). Cohort 2 comprised patients presenting acutely with possible cranial GCA (C-GCA) in whom the diagnosis was subsequently confirmed (C-GCA, n = 150) or excluded (Not C-GCA, n = 89). Proteomic findings were compared to published transcriptomic data from LVV-affected arteries.
RESULTS: In cohort 1, comparison to HCs revealed 52 differentially abundant proteins (DAPs) in TAK and 72 DAPs in LV-GCA. Within-case analyses identified 16 and 18 disease activity-associated proteins in TAK and LV-GCA, respectively. In cohort 2, comparing C-GCA versus not C-GCA revealed 31 DAPs. Analysis within C-GCA cases suggested the presence of distinct endotypes, with more pronounced proteomic changes in the biopsy-proven subgroup. Cross-comparison of TAK, LV-GCA, and biopsy-proven C-GCA revealed highly similar plasma proteomic profiles, with 26 shared DAPs including interleukin 6 (IL-6), monocyte/macrophage-related proteins (CCL7, CSF1), tissue remodeling proteins (TIMP1, TNC), and novel associations (TNFSF14, IL-7R). Plasma proteomic findings reflected LVV arterial phenotype; for 42% of DAPs, the corresponding gene was differentially expressed in tissue.
CONCLUSION: These findings suggest shared pathobiology across the LVV spectrum involving innate immunity, lymphocyte homeostasis, and tissue remodeling. Network-based analyses highlighted immune-stromal cross-talk and identified novel therapeutic targets (eg, TNFSF14).
Journal
Arthritis & Rheumatology