Heparin cofactor II-thrombin complex in MPS I: a biomarker of MPS disease.
The mucopolysaccharidoses are a clinically heterogeneous group of lysosomal storage disorders presenting with broad multi-system disease and a continuous range of phenotypes. Currently, there are no objective biomarkers of MPS disease that clearly reflect disease severity or therapeutic responsiveness. Using proteomic studies in the murine MPS I model, we have identified the formation of the heparin cofactor II-thrombin (HCII-T) complex, a well-known serine protease inhibitor (serpin)-serine protease complex, as an informative biomarker for MPS I. MPS I patients showed a range of serum HCII-T concentrations from 46,000-208,600 pM, whereas the control values varied from 115.1-398.0 pM. HCII-T complex was also elevated in plasma from MPS I patients and mice. The degree of HCII-T complex formation appears to correlate with disease severity and is responsive to therapy. In addition to its role as a biomarker, the discovery of increased serpin-serine protease complex formation provides a valuable insight into possible pathophysiological mechanisms of MPS disease.
Randall
Derrick R
DR
Department of Medical Genetics, University of British Columbia, Child and Family Research Institute, Vancouver, BC, Canada.
Sinclair
Graham B
GB
Colobong
Karen E
KE
Hetty
Elly
E
Clarke
Lorne A
LA
D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002648:Child; D005260:Female; D015844:Heparin Cofactor II / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008059:Mucopolysaccharidosis I / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding; D020543:Proteome / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*
D015415:Biomarkers; D020543:Proteome; D015844:Heparin Cofactor II; D013917:Thrombin