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Heparin cofactor II-thrombin complex in MPS I: a biomarker of MPS disease
Derrick R Randall1, Graham B Sinclair, Karen E Colobong
1Department of Medical Genetics, University of British Columbia, Child and Family Research Institute, Vancouver, BC, Canada.
Abstract:
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.
Insights
Researchers identified a new biomarker for Mucopolysaccharidoses (MPS) disease, the heparin cofactor II-thrombin (HCII-T) complex. This complex shows promise in reflecting MPS disease severity and response to therapy.
Area of Science:
- Biochemistry
- Genetics
- Medical Research
Background:
- Mucopolysaccharidoses (MPS) are a group of heterogeneous lysosomal storage disorders with diverse clinical presentations.
- Current diagnostic and monitoring tools for MPS lack objective biomarkers to accurately assess disease severity or treatment efficacy.
Purpose of the Study:
- To identify objective biomarkers for MPS disease that correlate with disease severity and therapeutic response.
- To investigate the potential of the heparin cofactor II-thrombin (HCII-T) complex as a biomarker for MPS I.
Main Methods:
- Proteomic studies were conducted using a murine model of MPS I.
- Serum and plasma samples from MPS I patients and control subjects were analyzed for HCII-T complex concentrations.
Main Results:
- The heparin cofactor II-thrombin (HCII-T) complex was identified as an informative biomarker in the murine MPS I model.
- Significantly elevated serum HCII-T concentrations were observed in MPS I patients compared to controls (46,000-208,600 pM vs. 115.1-398.0 pM).
- Elevated HCII-T complex levels were also found in plasma from MPS I patients and mice, correlating with disease severity and showing responsiveness to therapy.
Conclusions:
- The HCII-T complex is a promising objective biomarker for MPS I, reflecting disease severity and therapeutic responsiveness.
- The findings provide insights into potential pathophysiological mechanisms underlying MPS disease, specifically increased serpin-serine protease complex formation.
