Dysregulation of circulating collagen turnover markers in very early systemic sclerosis
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Dysregulation of circulating collagen turnover markers in very early systemic sclerosis. / Dobrota, Rucsandra; Jordan, Suzana; Juhl, Pernille; Del Papa, Nicoletta; Maurer, Britta; Becker, Mike; Mihai, Carina; Bay-Jensen, Anne C.; Karsdal, Morten Asser; Siebuhr, Anne Sofie; Distler, Oliver.
In: RMD Open, Vol. 10, No. 2, e003306, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Dysregulation of circulating collagen turnover markers in very early systemic sclerosis
AU - Dobrota, Rucsandra
AU - Jordan, Suzana
AU - Juhl, Pernille
AU - Del Papa, Nicoletta
AU - Maurer, Britta
AU - Becker, Mike
AU - Mihai, Carina
AU - Bay-Jensen, Anne C.
AU - Karsdal, Morten Asser
AU - Siebuhr, Anne Sofie
AU - Distler, Oliver
N1 - Publisher Copyright: © 2024 Authors.
PY - 2024
Y1 - 2024
N2 - Objective Clinical observation suggests that vascular activation and autoimmunity precede remodelling of the extracellular matrix (ECM) in systemic sclerosis (SSc). We challenge this paradigm by hypothesising that ECM biomarkers are already disturbed in patients with very early SSc (veSSc) when fibrosis is not yet clinically detectable. Methods 42 patients with veSSc, defined as the presence of Raynaud's phenomenon and at least one of puffy fingers, positive antinuclear antibodies or pathological nailfold capillaroscopy, not meeting the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for SSc, were compared with healthy controls (HCs, n=29). ECM degradation (BGM, C3M, C4M and C6M) and ECM formation biomarkers (PRO-C3, PRO-C4 and PRO-C5) were measured in serum using ELISAs. A cross-sectional analysis at baseline and a longitudinal analysis was performed. Results Compared with HC, veSSc patients showed a strongly dysregulated turnover of type III and IV collagens (higher C3M, C4M, both p<0.0001 and PRO-C3, p=0.004, lower turnover ratios PRO-C3/C3M and PRO-C4/C4M, both p<0.0001). The biglycan degradation biomarker BGM was higher in veSSc than in HC (p=0.006), whereas the degradation biomarker for type VI collagen, C6M, was lower (p=0.002). In an ROC analysis, biomarkers of type III and IV collagen excellently distinguished between veSSc and HC: C3M, AUC=0.95, p<0.0001; C4M, AUC=0.97, p<0.0001; turnover ratios PRO-C3/C3M, AUC=0.80, p<0.0001; PRO-C4/C4M, AUC=0.97; p<0.0001. Conclusion These findings indicate ECM remodelling as a very early phenomenon of SSc occurring in parallel with microvascular and autoimmune changes. Biomarkers of type III and IV collagens distinguished between veSSc patients and HC, indicating them as potential biomarkers for the detection of veSSc.
AB - Objective Clinical observation suggests that vascular activation and autoimmunity precede remodelling of the extracellular matrix (ECM) in systemic sclerosis (SSc). We challenge this paradigm by hypothesising that ECM biomarkers are already disturbed in patients with very early SSc (veSSc) when fibrosis is not yet clinically detectable. Methods 42 patients with veSSc, defined as the presence of Raynaud's phenomenon and at least one of puffy fingers, positive antinuclear antibodies or pathological nailfold capillaroscopy, not meeting the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for SSc, were compared with healthy controls (HCs, n=29). ECM degradation (BGM, C3M, C4M and C6M) and ECM formation biomarkers (PRO-C3, PRO-C4 and PRO-C5) were measured in serum using ELISAs. A cross-sectional analysis at baseline and a longitudinal analysis was performed. Results Compared with HC, veSSc patients showed a strongly dysregulated turnover of type III and IV collagens (higher C3M, C4M, both p<0.0001 and PRO-C3, p=0.004, lower turnover ratios PRO-C3/C3M and PRO-C4/C4M, both p<0.0001). The biglycan degradation biomarker BGM was higher in veSSc than in HC (p=0.006), whereas the degradation biomarker for type VI collagen, C6M, was lower (p=0.002). In an ROC analysis, biomarkers of type III and IV collagen excellently distinguished between veSSc and HC: C3M, AUC=0.95, p<0.0001; C4M, AUC=0.97, p<0.0001; turnover ratios PRO-C3/C3M, AUC=0.80, p<0.0001; PRO-C4/C4M, AUC=0.97; p<0.0001. Conclusion These findings indicate ECM remodelling as a very early phenomenon of SSc occurring in parallel with microvascular and autoimmune changes. Biomarkers of type III and IV collagens distinguished between veSSc patients and HC, indicating them as potential biomarkers for the detection of veSSc.
KW - autoimmune diseases
KW - collagen type VI
KW - connective tissue diseases
KW - systemic sclerosis
U2 - 10.1136/rmdopen-2023-003306
DO - 10.1136/rmdopen-2023-003306
M3 - Journal article
C2 - 38806188
AN - SCOPUS:85194878743
VL - 10
JO - RMD Open
JF - RMD Open
SN - 2056-5933
IS - 2
M1 - e003306
ER -
ID: 394987701