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Association of plasma levels of Protein S with disease severity in multiple sclerosis
Gerry Zm Ma1, Lauren L Giuffrida1, Melissa M Gresle2
1Multiple Sclerosis Division, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia.
Background:
The TAM family of receptor tyrosine kinases (TYRO3, AXL and MERTK) play important roles in modulating innate immune responses and central demyelination. The TAM receptor ligand Protein S (PROS) has also been shown to modulate innate immune cell responses.
Objectives:
We assessed whether plasma levels of PROS are changed in multiple sclerosis (MS) patients and whether changes are associated with disease severity.
Methods:
Plasma levels of total and free PROS were measured using enzyme-linked immunosorbent assay in a discovery cohort (MS: 65, control: 14) and an independent replication cohort (MS: 29, control: 29). The Multiple Sclerosis Severity Score (MSSS) was used to evaluate associations between plasma PROS levels and disease severity.
Results:
We found plasma levels of total, but not free PROS, were decreased in MS patients compared with controls. In female MS patients, we observed decreases in total and free PROS levels compared with controls. In addition, we also observed higher MSSS in patients with very low levels of plasma free PROS.
Conclusions:
These data suggest PROS may represent a potential marker of disease severity in MS.
Insights
Plasma levels of Protein S (PROS) are decreased in multiple sclerosis (MS) patients. Lower PROS levels correlate with increased MS disease severity, suggesting PROS as a potential biomarker.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
Background:
- The TAM family of receptor tyrosine kinases (TYRO3, AXL, MERTK) are crucial in innate immunity and central nervous system demyelination.
- Protein S (PROS), a ligand for TAM receptors, influences innate immune cell responses.
Purpose of the Study:
- To investigate alterations in plasma PROS levels in multiple sclerosis (MS) patients.
- To determine if changes in PROS levels correlate with MS disease severity.
Main Methods:
- Plasma levels of total and free PROS were quantified using enzyme-linked immunosorbent assay (ELISA).
- Two cohorts were utilized: a discovery cohort (65 MS, 14 control) and a replication cohort (29 MS, 29 control).
- The Multiple Sclerosis Severity Score (MSSS) assessed disease severity in relation to PROS levels.
Main Results:
- Total PROS levels were significantly decreased in MS patients compared to controls.
- Female MS patients exhibited reduced levels of both total and free PROS.
- Very low plasma free PROS levels were associated with higher MSSS, indicating greater disease severity.
Conclusions:
- Plasma PROS levels are altered in multiple sclerosis.
- PROS may serve as a potential biomarker for assessing MS disease severity.
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