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The MMP-9/TIMP-1 Ratio and Concentrations of Osteopontin Are Elevated in Cerebrospinal Fluid of People With Multiple
Ivan Pavlovic1, Ida Erngren2, Kim Kultima2
1Translational Neurology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Objectives:
To evaluate the utility of cerebrospinal fluid (CSF) biomarkers-matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), the MMP-9/TIMP-1 ratio, and osteopontin (OPN)-as indicators of blood-brain barrier (BBB) integrity and disease activity in people with relapsing-remitting multiple sclerosis (pwMS), and to assess their changes following autologous hematopoietic stem cell transplantation (aHSCT).
Methods:
CSF samples from pwMS treated with aHSCT (n = 43) and healthy controls (n = 32) were analyzed for MMP-9, TIMP-1, and OPN concentrations using ELISA and electrochemiluminescence assays. Lumbar punctures were performed at baseline and at 1, 2, and 3-5 years post-aHSCT. Biomarker findings were compared with standard CSF parameters, prior treatments, and MRI data.
Results:
MMP-9/TIMP-1 ratios and OPN levels were significantly elevated in pwMS compared to controls, particularly in those with gadolinium-enhancing lesions or on first-line therapies. Both biomarkers declined significantly after aHSCT and remained low during follow-up. The MMP-9/TIMP-1 ratio showed superior discriminatory capacity and correlated with inflammatory CSF markers.
Interpretation:
CSF MMP-9/TIMP-1 ratio and OPN are elevated in MS and decrease following aHSCT, reflecting reduced inflammation and restored BBB integrity. These biomarkers may support disease monitoring and therapeutic evaluation.
