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Updated: Apr 17, 2026
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in
Alessandro Trentini1, Maria C Manfrinato1, Massimiliano Castellazzi1
1Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Italy.
Background:
The activity of matrix metalloproteinase-9 (MMP-9) depends on two isoforms, an 82 kDa active MMP-9 modulated by its specific tissue inhibitor (TIMP-1), and a 65 kDa TIMP-1 resistant active MMP-9. The relevance of these two enzymatic isoforms in multiple sclerosis (MS) is still unknown.
Objective:
To investigate the contribution of the TIMP-1 modulated and resistant active MMP-9 isoforms to MS pathogenesis.
Methods:
We measured the serum levels of the 82 kDa and TIMP-1 resistant active MMP-9 isoforms by activity assay systems in 86 relapsing-remitting MS (RRMS) patients, categorized according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, and in 70 inflammatory (OIND) and 69 non-inflammatory (NIND) controls.
Results:
Serum levels of TIMP-1 resistant MMP-9 were more elevated in MS patients than in OIND and NIND (p < 0.05, p < 0.02, respectively). Conversely, 82 kDa active MMP-9 was higher in NIND than in the OIND and MS patients (p < 0.01 and p < 0.00001, respectively). MRI-active patients had higher levels of TIMP-1 resistant MMP-9 and 82 kDa active MMP-9, than did those with MRI inactive MS (p < 0.01 and p < 0.05, respectively).
Conclusion:
Our findings suggested that the TIMP-1 resistant MMP-9 seem to be the predominantly active isoform contributing to MS disease activity.
Insights
The TIMP-1 resistant matrix metalloproteinase-9 (MMP-9) isoform is elevated in multiple sclerosis (MS) patients and correlates with disease activity. This suggests its significant role in MS pathogenesis, unlike the TIMP-1 modulated isoform.
Area of Science:
- Neuroimmunology
- Enzymology
- Biochemistry
Background:
- Matrix metalloproteinase-9 (MMP-9) exists in two active isoforms: 82 kDa (TIMP-1 modulated) and 65 kDa (TIMP-1 resistant).
- The distinct roles of these MMP-9 isoforms in multiple sclerosis (MS) pathogenesis remain unclear.
Purpose of the Study:
- To investigate the specific contribution of TIMP-1 modulated and TIMP-1 resistant active MMP-9 isoforms to the pathogenesis of MS.
- To differentiate the roles of MMP-9 isoforms in disease activity within MS patients.
Main Methods:
- Serum levels of 82 kDa and TIMP-1 resistant active MMP-9 were quantified using activity assay systems.
- Study included 86 relapsing-remitting MS (RRMS) patients, 70 other inflammatory neurological disease (OIND) controls, and 69 non-inflammatory (NIND) controls.
- MS patients were stratified based on clinical and MRI evidence of disease activity.
Main Results:
- Serum levels of TIMP-1 resistant MMP-9 were significantly higher in MS patients compared to both OIND and NIND groups.
- Conversely, 82 kDa active MMP-9 levels were elevated in NIND patients compared to OIND and MS patients.
- Patients with active MS (based on MRI) exhibited higher levels of both TIMP-1 resistant and 82 kDa active MMP-9 compared to MRI-inactive MS patients.
Conclusions:
- The TIMP-1 resistant MMP-9 isoform appears to be the primary active form implicated in MS disease activity.
- These findings highlight the differential roles of MMP-9 isoforms in neurological disease.
- Further research into MMP-9 isoform-specific functions could inform MS therapeutic strategies.
