Axial spondyloarthritis, psoriatic arthritis and systemic lupus erythematosus share common molecular features based on post-hoc analysis of serum biomarkers.
Abstract
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) (n = 66), PsA (NCT03158285) (n = 267) and SLE (NCT02349061) (n = 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 (k = 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 (p <0.003) in r-axSpA, PsA and SLE patients versus healthy donors. Serum C10C marker was elevated up to 1.2-fold (p < 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 (p < 0.025) versus healthy donors. Three endotypes were identified: 1) hypertrophic (n = 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 (n = 156), with high tissue degradation, increased PRO-C4 and severe inflammation with elevated disease activity; 3) fibrogenic (n = 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.
