Role of matrix metalloproteinase-3 (MMP-3) and magnetic resonance imaging of sacroiliitis in assessing disease activity in ankylosing spondylitis

Abstract

The objective of this study is to evaluate the role of MMP-3 and MRI in assessing disease activity in sacroiliac joints of AS patients in comparison to the conventional measures Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Serum MMP-3 was measured in 30 patients who fulfilled the modified New York criteria for AS and in ten healthy volunteers. AS patients were categorized into those having high or low MMP-3 according to a cut-off value = 7.1 ng/ml. MRI of the sacroiliac joints (SIJs) was performed on all patients. SIJs were evaluated for enhancement and subchondral bone marrow edema. Results of MMP-3 and findings on MRI were correlated with multiple clinical parameters including BASDAI, ESR and CRP. Serum MMP-3 was significantly elevated in AS patients with active disease. Elevated MMP-3 levels were significantly associated with high BASDAI (P = 0.046), but not with ESR or CRP. MRI showed bone marrow edema and enhancement of SIJs in 19/30 patients with one patient showing enhancement only. These MRI findings were not correlated with MMP-3, BASDAI, CRP or ESR. In conclusion, serum MMP-3 is an objective measure reflecting clinical disease activity in AS. Bone marrow edema and enhancement detected by MRI of SIJs is another objective measure of disease activity, but are not correlated with MMP-3 or the conventional parameters as BASDAI, ESR, or CRP. Although both MMP-3 and MRI can reflect disease activity in AS they seem to be unrelated, perhaps each is reflecting a different aspect of disease activity. MMP-3 and MRI should be considered together with BASDAI in assessing disease activity and in guiding the available recommendations for initiation of biologics in AS.

Biomarkers, imaging and disease activity indices in patients with early axial spondyloarthritis: the Italian arm of the SpondyloArthritis-Caught-Early (SPACE) Study

“…The correlation between serological MMP3 levels and mSASSS, indicative of the role of metalloproteinases in the bone formation process, was an interesting finding and in accordance with data outlined by Maksymowych et al (47) who reported that independently of other indices, serum MMP3 levels were able to predict two-year radiographic progression in the 97 axSpA patients studied. Our data also showed that MMP3 is correlated with inflammatory markers (hs-CRP and ESR) and, in agreement with previous studies, it is increased in the serum of patients with active axSpA (24,26,27,47). The correlations between mSASS values and serum biomarkers require further evaluation by prospective studies.…”

“…Recent studies have focused on the role of other biomarkers to diagnose early-stage axSpA, to evaluate DA, and to predict patients at higher risk of worse outcome (16,17). Among these, matrix metalloproteinase (MMP) markers (and, in particular, MMP3) have also been considered possible biomarkers of DA given the correlation between MMP3 and CRP, DA and functional indices, such as BAS-DAI and Bath Ankylosing Spondylitis Functional Index (BASFI) (17,(24)(25)(26), and of the radiographic progression in AS patients (27). Although serum MMP3 represents a reliable parameter of DA, there is often no correlation with inflammatory MRI findings (26).…”

“…Among these, matrix metalloproteinase (MMP) markers (and, in particular, MMP3) have also been considered possible biomarkers of DA given the correlation between MMP3 and CRP, DA and functional indices, such as BAS-DAI and Bath Ankylosing Spondylitis Functional Index (BASFI) (17,(24)(25)(26), and of the radiographic progression in AS patients (27). Although serum MMP3 represents a reliable parameter of DA, there is often no correlation with inflammatory MRI findings (26). The aim of the current study was to examine some serological biomarkers, clinical and imaging parameters and DA indices in patients with early axSpA who were participating in the Italian arm of the SpondyloArthritis Caught Early (SPACE) study.…”

Serum matrix metalloproteinases-3 levels in patients with ankylosing spondylitis

“…Two additional studies were removed after further assessment. Finally, 13 case-control studies were analyzed in the current meta-analysis (Yang et al, 2004b;Chen et al, 2006;de Seny et al, 2008;Lin et al, 2008;Sun and Yang, 2008;Wendling et al, 2008;Wang et al, 2010;Shen et al, 2011;Ma and Yang, 2012;Soliman et al, 2012;Dhir et al, 2013;Sha and Lei, 2013;Hou et al, 2014).…”

“…However, other related documents indicated no correlation between serum MMP-3 levels and AS pathogenesis (Lin et al, 2008;Soliman et al, 2012). Therefore, the present meta-analysis aggregated previous findings from relevant studies in an attempt to systematically assess the relationship between serum MMP-3 levels and the etiology of AS.…”