The levels of the serine protease HTRA1 in cerebrospinal fluid correlate with progression and disability in multiple sclerosis

Background High Temperature Requirement Serine Protease A1 (HTRA1) degrades extracellular matrix molecules (ECMs) and growth factors. It interacts with several proteins implicated in multiple sclerosis (MS), but has not previously been linked to the disease. Objective Investigate the levels of HTRA1 in cerebrospinal fluid (CSF) in different subtypes of MS and brain tissue. Methods Using ELISA, HTRA1 levels were compared in CSF from untreated patients with relapsing-remitting MS (RRMS, n = 23), secondary progressive MS (SPMS, n = 26) and healthy controls (HCs, n = 26). The effect of disease modifying therapies (DMTs) were examined in both patient groups. Cellular distribution in human brain was studied using immunochemistry and the oligointernode database, based on a single-nuclei RNA expression map. Results HTRA1 increased in RRMS and SPMS compared to HCs. DMT decreased HTRA1 levels in both types of MS. Using ROC analysis, HTRA1 cut-offs could discriminate HCs from RRMS patients with 100% specificity and 82.6% sensitivity. In the brain, HTRA1 was expressed in glia and neurons. Conclusion HTRA1 is a promising CSF biomarker for MS correlating with disease- and disability progression. Most cell species of the normal and diseased CNS express HTRA1 and the expression pattern could reflect pathological processes involved in MS pathogenesis.

Sejbaek, T. (author)
Axelsson, Markus,1975Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience(Swepub:gu)xaxmar (author)
Vinslov-Jensen, H. (author)
Mortensen, S. K. (author)
Pihl-Jensen, G. (author)
Novakova, Lenka,1984Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience(Swepub:gu)xnovle (author)
Christensen, J. D. R. (author)
Pedersen, C. B. (author)
Halle, B. (author)
Poulsen, F. R. (author)
Frederiksen, J. L. (author)
Zhang, M. L. (author)
Benedikz, E. (author)
Lycke, Jan,1956Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience(Swepub:gu)xlycja (author)
Illes, Z. (author)
Svenningsen, A. F. (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap (creator_code:org_t)

In:Journal of Neurology: Springer Science and Business Media LLC268, s. 3316-33240340-53541432-1459

By the author/editor: Hjaeresen, S.; Sejbaek, T.; Axelsson, Markus ...; Vinslov-Jensen, ...; Mortensen, S. K.; Pihl-Jensen, G.; show more...; Novakova, Lenka, ...; Christensen, J. ...; Pedersen, C. B.; Halle, B.; Poulsen, F. R.; Frederiksen, J. ...; Zhang, M. L.; Benedikz, E.; Lycke, Jan, 1956; Illes, Z.; Svenningsen, A. ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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