title: Heparin cofactor II-thrombin complex and dermatan sulphate:chondroitin sulphate ratio are biomarkers of short- and long-term treatment effects in mucopolysaccharide diseases.
abstract: Early detection of mucopolysaccharidosis (MPS) is an important factor in treatment success; therefore, good disease biomarkers are vital. We evaluate heparin cofactor II-thrombin complex (HCII-T) as a biomarker in serum and dried blood spots (DBS) of MPS patients. Serum HCII-T and urine dermatan sulphate:chondroitin sulphate (DS:CS) ratio are also compared longitudinally against clinical outcomes in MPSI, II and VI patients following treatment. Samples were collected from MPS patients at the Royal Manchester Children's Hospital. DS:CS ratio was obtained by measuring the area density of spots from 2D electrophoresis of urinary glycosaminoglycans. Serum and DBS HCII-T was measured by sandwich ELISA. Serum HCII-T is elevated approximately 25-fold in MPS diseases that store DS, clearly distinguishing untreated MPSI, II and VI patients from unaffected age-matched controls. Serum HCII-T is also elevated in MPSIII, which leads to storage of heparan sulphate, with an increase of approximately 4-fold over unaffected age-matched controls. Urine DS:CS ratio and serum HCII-T decrease in response to treatment of MPSI, II and VI patients. HCII-T appears to respond rapidly to perturbations in treatment, whilst DS:CS ratio responds more slowly. HCII-T is a suitable biomarker for MPSI, II and VI, and it may also be informative for MPS diseases storing HS alone, such as MPSIII, although the elevation observed is smaller. In treated MPS patients, HCII-T and DS:CS ratio appear to measure short-term and long-term treatment outcomes, respectively. The potential value of HCII-T measurement in DBS for newborn screening of MPS diseases warrants further investigation.
authors.affiliation: MPS Stem Cell Research Group, Faculty of Medical and Human Sciences, University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Kia Jane
authors.initials: KJ
authors.lastname: Langford-Smith
authors.forename: Jean
authors.initials: J
authors.lastname: Mercer
authors.forename: June
authors.initials: J
authors.lastname: Petty
authors.forename: Karen
authors.initials: K
authors.lastname: Tylee
authors.forename: Heather
authors.initials: H
authors.lastname: Church
authors.forename: Jane
authors.initials: J
authors.lastname: Roberts
authors.forename: Gill
authors.initials: G
authors.lastname: Moss
authors.forename: Simon
authors.initials: S
authors.lastname: Jones
authors.forename: Rob
authors.initials: R
authors.lastname: Wynn
authors.forename: J Ed
authors.initials: JE
authors.lastname: Wraith
authors.forename: Brian W
authors.initials: BW
authors.lastname: Bigger
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002809:Chondroitin Sulfates / Q000737:chemistry*; D003871:Dermatan Sulfate / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006025:Glycosaminoglycans / Q000378:metabolism* / Q000652:urine; D015844:Heparin Cofactor II / Q000737:chemistry*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D015997:Neonatal Screening / Q000379:methods; D013917:Thrombin / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans; D003871:Dermatan Sulfate; D015844:Heparin Cofactor II; D002809:Chondroitin Sulfates; D013917:Thrombin