TY - JOUR
T1 - The levels of the serine protease HTRA1 in cerebrospinal fluid correlate with progression and disability in multiple sclerosis
AU - Hjæresen, Simone
AU - Sejbaek, Tobias
AU - Axelsson, Marcus
AU - Vinsløv-Jensen, Helle
AU - Mortensen, Sif Kløvedal
AU - Pihl-Jensen, Gorm
AU - Novakova, Lenka
AU - Christensen, Julie Damgaard Rosgaard
AU - Pedersen, Christian Bonde
AU - Halle, Bo
AU - Poulsen, Frantz Rom
AU - Lautrup Frederiksen, Jette
AU - Zhang, Mengliang
AU - Benedikz, Eirikur
AU - Lycke, Jan
AU - Illes, Zsolt
AU - Fex Svenningsen, Åsa
N1 - © 2021. Springer-Verlag GmbH, DE part of Springer Nature.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - Biomarkers/chemistry
KW - Case-Control Studies
KW - Disease Progression
KW - High-Temperature Requirement A Serine Peptidase 1/cerebrospinal fluid
KW - Humans
KW - Multiple Sclerosis, Chronic Progressive/cerebrospinal fluid
KW - Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid
UR - http://www.scopus.com/inward/record.url?scp=85101920593&partnerID=8YFLogxK
U2 - 10.1007/s00415-021-10489-7
DO - 10.1007/s00415-021-10489-7
M3 - Journal article
C2 - 33661357
SN - 0340-5354
VL - 268
SP - 3316
EP - 3324
JO - Journal of Neurology
JF - Journal of Neurology
IS - 9
ER -