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Published on: July 23, 2012
Reduced expression of membrane-bound (m)RAGE is a biomarker of multiple sclerosis disease progression
Zohara Sternberg1, Anne Chiotti1, Joseph Tario2
1Department of Neurology, Baird MS Center, Jacobs Neurological Institute, Buffalo, NY, USA.
Objectives:
This study is one in series measuring RAGE axis (receptor for advanced glycation end products, its isoforms, and ligands) as a biomarker in multiple sclerosis (MS). We identified and quantified membrane-bound RAGE (mRAGE) expression levels on freshly isolated PBMCs and its subpopulation (monocytes and T cells), and determined the relationship between mRAGE expression levels and MS disease severity.
Materials And Methods:
mRAGE expression was determined for 28 MS patients and 16HCs, by flow cytometry, using fluorochrome unconjugated primary RAGE monoclonal antibody and a polyclonal secondary antibody conjugated to R-Phycoerythrin (PE).
Results:
After adjusting for multiple comparisons and correcting for group differences in age and gender, MS patients showed higher percentages of mRAGE-positive on PBMCs (12.4±2.1 vs. 4.08±0.8, P=0.02), monocytes (37.4±5.8 vs. 20.1±5.0, P=0.08) and T cells (4.1±1.2 vs. 2.1±0.3, P=0.05). SPMS patients' showed lower percentages of RAGE-positive monocytes (13.7±5.5 vs. 49.5±6.6, P=0.0006) and RAGE-positive T cells (4.1±1.8 vs. 6.6±1.5, P=0.04) than RRMS patients. We observed a negative relationship between the percentages of mRAGE-positive PBMCs and MS severity scale (MSSS) (r=-0.39, P=0.04), monocytes and EDSS (r=-0.48, P=0.01), monocytes and MSSS (r=-0.58, P=0.001), and T cells and MSSS (r=-0.40, P=0.04). Monocytes expression of mRAGE showed 0.811 area under the curve (95% CI: 0.64-0.98) sensitivity/specificity for MSSS.
Conclusion:
The reduced mRAGE expression on PBMCs in general, and on monocytes in particular, can be used as biomarker of MS disease severity and progression.
Insights
Reduced expression of membrane-bound RAGE (mRAGE) on peripheral blood mononuclear cells (PBMCs) and monocytes indicates multiple sclerosis (MS) disease severity. This finding suggests mRAGE is a potential biomarker for MS progression.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
- Cellular Immunology
Background:
- The receptor for advanced glycation end products (RAGE) axis is implicated in multiple sclerosis (MS) pathogenesis.
- Understanding RAGE expression in MS is crucial for identifying novel biomarkers.
Purpose of the Study:
- To quantify membrane-bound RAGE (mRAGE) expression on peripheral blood mononuclear cells (PBMCs) and their subpopulations (monocytes, T cells) in MS patients.
- To investigate the correlation between mRAGE levels and MS disease severity.
Main Methods:
- Flow cytometry was used to measure mRAGE expression on PBMCs, monocytes, and T cells from 28 MS patients and 16 healthy controls (HCs).
- Statistical analyses were performed, including adjustments for age and gender, and correlation analyses with MS severity scales (MSSS, EDSS).
Main Results:
- MS patients exhibited higher percentages of mRAGE-positive PBMCs, monocytes, and T cells compared to HCs.
- Secondary progressive MS (SPMS) patients showed lower mRAGE expression on monocytes and T cells than relapsing-remitting MS (RRMS) patients.
- A negative correlation was observed between mRAGE expression on PBMCs, monocytes, T cells and MS severity scores (MSSS, EDSS). Monocyte mRAGE expression demonstrated good sensitivity and specificity for MSSS.
Conclusions:
- Reduced mRAGE expression on PBMCs, particularly monocytes, serves as a potential biomarker for MS disease severity and progression.
- mRAGE quantification offers a valuable tool for monitoring MS.
- Further research into the RAGE axis in MS is warranted.
