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Abstract
Background Axial spondyloarthritis (axSpA) comprises two groups - radiographic (r-axSpA) and non-radiographic (nr-axSpA) with varying disease activity, spine involvement and response to biological therapy. An objective biomarker of disease activity may be able to select patients, which will benefit from a given biological treatment.
Objectives We investigated the association of extracellular matrix (ECM) degradation biomarkers in axSpA patients (r-axSpA and nr-axSpA) with disease activity.
Methods AxSpA patients (n=193; 72 r-axSpA and 121 nr-axSpA) and 100 healthy controls were included in the study. Biomarkers of type I, II, III and IV degradation (C1M, C2M, C3M, C4M2), MMP-degraded CRP (CRPM) and MMP-degraded and citrullinated vimentin (VICM) were detected by ELISA in serum. Mann-Whitney t-test tested the difference in the biomarker levels between groups and multiple regression analysis investigated the association between biomarkers and clinical manifestations with adjustment for age, gender, BMI, disease duration and CRP. ROC AUC tested the biomarkers capacity to differentiate the patient groups.
Results Patients with r-axSpA compared to nr-axSpA patients had higher radiographic status and longer disease duration (p<0.001), whereas nr-axSpA had more swollen joints (p=0.0093). They were alike in age, BMI and disease activity (ASDAS-CRP, BASDAI and HAQ). All tested biomarkers except VICM were elevated in the axSpA patients compared to healthy subjects (all p<0.001). VICM was lower in the axSpA group, particularly in nr-axSpA compared to healthy (p=0.036 and p=0.002 respectively). R-axSpA compared to nr-axSpA patients had higher level of C1M, C3M, C4M2, CRPM and VICM (p<0.001, =0.001, <0.001, <0.001 and =0.003), but not C2M (p=0.92). C1M correlated to ASDAS-CRP in both r-axSpA and nr-axSpA (r-partiel: 0.46 and 0.44) with adjustment for age, gender, BMI and disease duration, but the correlation was lost by adjustment for CRP. Also C3M and C4M2 correlated to ASDAS-CRP in both axSpA groups. C2M was in r-axSpA patients moderately correlated to ASDAS-CRP, but minimal after adjustment of CRP (r-partiel: 0.32 unadjusted and 0.18 adjusted). CRPM correlated to ASDAS-CRP with adjustment to CRP in r-axSpA (r-partiel: 0.27 unadjusted, 0.26 adjusted), but not in nr-axSpA (r-partiel: 0.19 unadjusted, 0.03 adjusted).
Especially, C3M and C4M2 could differentiate between healthy and the axSpA patients (AUC 0.95 and 0.89), but also C1M, C2M, CRPM had AUC of ≥0.72. VICM was the only biomarker to differ between r-axSpA (AUC 0.92 and nr-axSpA (AUC 0.51).
Conclusions Biomarkers of ECM turnover, C3M and C4M2 in particular, were associated with r-axSpA and nr-axSpA and could define disease. The biomarkers of ECM degradation, especially C1M, may reflect the pathogenetic background of axSpA.
Acknowledgements Supported by Project for Conceptual development of MH CR – Inst. of Rheumatology (no.023728).
Disclosure of Interest A. S. Siebuhr Employee of: Nordic Bioscience, A.-C. Bay-Jensen Employee of: Nordic Bioscience, K. Pavelka: None declared, S. Forejtova: None declared, K. Zegzulkova: None declared, M. Tomcik: None declared, M. Karsdal Shareholder of: Nordic Bioscience, Employee of: Nordic Bioscience, M. Urbanova: None declared, K. Grobelna: None declared, J. Horinkova: None declared, J. Gatterova: None declared, M. Husakova: None declared