Maughan, R.T., MacDonald-Dunlop, E., Haroon-Rashid, L. et al. (13 more authors) (2025) Proteomic profiling of the large-vessel vasculitis spectrum identifies shared signatures of innate immune activation and stromal remodelling. Arthritis & Rheumatology. ISSN 2326-5191
Abstract
Background
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 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 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 IL6, monocyte/macrophage related proteins (CCL7, CSF1), tissue remodelling proteins (TIMP1, TNC) and novel associations (TNFSF14, IL7R). Plasma proteomic findings reflected LVV arterial phenotype; for 42% of DAPs, the corresponding gene was differentially expressed in tissue.
Conclusions
These findings suggest shared pathobiology across the LVV spectrum involving innate immunity, lymphocyte homeostasis and tissue remodelling. Network-based analyses highlighted immune-stromal crosstalk and identified novel therapeutic targets (e.g. TNFSF14).
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This is an author produced version of an article published in Arthritis & Rheumatology, made available under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number NIHR National Inst Health Research Not Known NIHR National Inst Health Research NIHR202395 MRC (Medical Research Council) MR/N011775/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Jan 2025 13:00 |
Last Modified: | 27 Jan 2025 15:39 |
Status: | Published online |
Publisher: | Wiley |
Identification Number: | 10.1002/art.43110 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221574 |