BibTex format
@article{Maughan:2025,
author = {Maughan, R and Macdonald-Dunlop, E and Haroon-Rashid, L and Sorensen, L and Chaddock, N and Masters, S and Porter, A and Peverelli, M and Pericleous, C and Hutchings, A and Robinson, J and Youngstein, T and Luqmani, R and Mason, J and Morgan, A and Peters, J},
journal = {Arthritis & Rheumatology},
title = {Proteomic profiling of the large-vessel vasculitis spectrum identifies shared signatures of innate immune activation and stromal remodelling},
year = {2025}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - 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).
AU - Maughan,R
AU - Macdonald-Dunlop,E
AU - Haroon-Rashid,L
AU - Sorensen,L
AU - Chaddock,N
AU - Masters,S
AU - Porter,A
AU - Peverelli,M
AU - Pericleous,C
AU - Hutchings,A
AU - Robinson,J
AU - Youngstein,T
AU - Luqmani,R
AU - Mason,J
AU - Morgan,A
AU - Peters,J
PY - 2025///
SN - 2326-5191
TI - Proteomic profiling of the large-vessel vasculitis spectrum identifies shared signatures of innate immune activation and stromal remodelling
T2 - Arthritis & Rheumatology
ER -