Axial spondyloarthritis, psoriatic arthritis and systemic lupus erythematosus share common molecular features based on post-hoc analysis of serum biomarkers

Malmkvist, Rikke; Bay-Jensen, Anne-Christine; Sinkeviciute, Dovile; Nielsen, Signe Holm; Hannani, Monica Toft; Frederiksen, Peder; Karsdal, Morten Asser; Gao, Sheng; Chen, Warner

doi:10.1007/s00296-025-06012-0

Table 1 Overview of tissue-remodelling biomarkers investigated in this study

From: Axial spondyloarthritis, psoriatic arthritis and systemic lupus erythematosus share common molecular features based on post-hoc analysis of serum biomarkers

Biomarker	Analyte	Description
C1M	Type I α1 collagen fragments generated by MMP-1, -2, -8, -13 and -14 [17]	Reflects connective tissue destruction. Elevated across multiple disease in the inflammatory space including PsA, axSpA and RA [18,19,20]
C2M	Type II collagen fragments generated by multiple MMPs [21].	Reflects cartilage degradation. Released from cartilage in response to proinflammatory cytokines such as TNF [21]
C3M	Type III collagen fragments generated mainly by MMP-9 [22]	Reflects interstitial matrix degradation. Elevated across multiple disease in the fibroinflammatory space including PsA, axSpA and RA [10, 18, 19]
C4M	Type IV collagen fragments generated mainly by MMP-2 and -9 [22]	Reflects basement membrane degradation. Elevated across multiple disease in inflammatory space including RA and SSc [9, 18]
C6M	Type VI collagen fragments generated mainly by MMP-2 and -9 [23]	Reflects interstitial matrix degradation. Elevated across multiple disease in fibroinflammatory space including axSpA and SSc [19, 24]
C10C	Type X collagen fragments generated by cathepsin K (NC1 domain) [25]	Reflects endochondral bone modelling/remodelling. Produced by hypertrophic chondrocytes. Elevated in OA, PsA and axSpA [25, 26]
PRO-C1	The N-terminal propeptide of type I collagen [27]	Reflects both bone modelling/remodelling and fibrosis. Lowered levels observed in SSc [24]
PRO-C2	The N-terminal propeptide of type II collagen (PIIBNP) [28]	Reflects cartilage formation. Lower in OA and elevated in axSpA and PsA [26, 29]
PRO-C3	The N-terminal propeptide of type III collagen (PIIINP) [30]	Reflects connective fibrogenesis. Elevated in SSc and PsA [10, 24]
PRO-C4	The type VI collagen 7S domain [31]	Reflects basement membrane remodelling. Elevated in SSc [24]
PRO-C6	The C-terminus cleavage of type VI collagen (C5 domain, endotrophin) [32]	Reflects interstitial matrix formation. Elevated in SSc and PsA [10, 24]
VICM	Citrullinated and MMP degraded fragment of vimentin [33]	Reflects mononuclear cell activation, mainly macrophages. Elevated in RA and axSpA [18, 34]

References are selected as examples of the signal observed for disease compared to healthy controls in the fibroinflammatory space with focus on rheumatology
axSpA Axial Spondyloarthritis, MMP Matrix metalloproteinases, OA Osteoarthritis, PsA Psoriatic Arthritis, RA Rheumatoid Arthritis, SSc Systemic Sclerosis, TNF Tumour necrosis factor

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