Axial spondyloarthritis, psoriatic arthritis and systemic lupus erythematosus share common molecular features based on post-hoc analysis of serum biomarkers.
Abstract
UNLABELLED
Axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and systemic lupus erythematosus (SLE) are distinct rheumatological diseases with common molecular features. This study explored tissue-associated remodelling endotypes using blood-based biomarkers reflecting interstitial matrix and basement membrane remodelling. Baseline serum samples from radiographic axSpA (r-axSpA) (NCT02437162/NCT02438787) (= 66), PsA (NCT03158285) (= 267) and SLE (NCT02349061) (= 97) studies were analysed alongside healthy donors. Biomarkers of collagen turnover (C1M, C2M, C3M, C4M, C6M, C10C, PRO-C1, PRO-C2, PRO-C3, PRO-C4, PRO-C6) were measured by immunoassays and compared using Kruskal-Wallis tests. K-means clustering (= 3) of r-axSpA, PsA and SLE patients was applied to construct disease endotype clusters. Serum C1M, C3M, C4M, C6M, and PRO-C3 markers were elevated up to 4.2-fold (<0.003) in r-axSpA, PsA and SLE patients versus healthy donors. Serum C10C marker was elevated up to 1.2-fold (< 0.001) in PsA and SLE patients versus healthy donors. PsA and r-axSpA patients showed increased levels of serum PRO-C2, PRO-C4, and PRO-C6 up to 1.4-fold (< 0.025) versus healthy donors. Three endotypes were identified: 1) hypertrophic (= 171), with elevated C10C, low PRO-C4 and lower disease activity reflected by CRP, ASDAS (r-axSpA), PASI, DAS28 (PsA) and joint scores (SLE); 2) fibrolytic (= 156), with high tissue degradation, increased PRO-C4 and severe inflammation with elevated disease activity; 3) fibrogenic (= 93), with increased cartilage degradation (C2M), fibrosis (PRO-C3, PRO-C6) and moderate disease activity. Tissue-associated remodelling profiles highlight heterogeneity within each disease and common molecular features, revealing clinically relevant subgroups. Identifying biomarker endotypes may guide targeted treatments and inform drug repurposing across rheumatological diseases.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s00296-025-06012-0.
