title: Soluble thrombomodulin levels in plasma of multiple sclerosis patients and their implication.
abstract: Thrombomodulin (TM) on the cell-surface of cerebrovascular endothelial cells (CECs) is released into blood upon CEC damage. TM promotes activation of protein C (APC), an anticoagulant, anti-inflammatory, neuroprotective molecule that protects CECs and impedes inflammatory cell migration across the blood-brain barrier (BBB). Multiple sclerosis (MS) is associated with CEC damage and BBB dysfunction. We evaluated soluble TM (sTM) levels as a biomarker of BBB integrity and whether glatiramer acetate (GA) influenced sTM levels in MS patients. sTM levels quantified by 2-site ELISA from sera of healthy controls and systemic lupus erythematosus (SLE) patients (CEC-damage positive control) were compared with levels from patients with relapsing-remitting (RRMS) or secondary-progressive MS (SPMS), stratified as: RRMS/GA/no relapse, RRMS/GA/in relapse, RRMS no GA/no relapse, RRMS/no GA/in relapse; and SPMS/no GA. Additionally, soluble endothelial protein C receptor (sEPCR) levels were assessed in the non-stratified MS group, SLE patients, and controls. sTM levels were highest in RRMS patients taking GA with or without relapse, followed in decreasing order by SLE, RRMS/no GA/in relapse, SPMS, RRMS/no GA/no relapse, healthy controls. sEPCR levels were highest in MS patients, then SLE, then controls. sTM may be a useful biomarker of BBB integrity in RRMS patients. Further evaluation of sEPCR is needed. The finding that the highest sTM levels were in RRMS patients taking GA is interesting and warrants further investigation.
authors.affiliation: Neurobiology Research Laboratory, Veterans Affairs Medical Center, Kansas City, MO 64128, USA. bfestoff@kumc.edu
authors.forename: Barry W
authors.initials: BW
authors.lastname: Festoff
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Li
authors.forename: Barry
authors.initials: B
authors.lastname: Woodhams
authors.forename: Sharon
authors.initials: S
authors.lastname: Lynch
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers; D001812:Blood-Brain Barrier; D000074283:Endothelial Protein C Receptor; D004730:Endothelium, Vascular / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood* / Q000188:drug therapy; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000188:drug therapy; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000097:blood; D012995:Solubility; D018180:Thrombomodulin / Q000097:blood* / Q000502:physiology
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D010455:Peptides; D011956:Receptors, Cell Surface; C546931:THBD protein, human; D018180:Thrombomodulin; D000068717:Glatiramer Acetate