title: Reduced expression of membrane-bound (m)RAGE is a biomarker of multiple sclerosis disease progression.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  The reduced mRAGE expression on PBMCs in general, and on monocytes in particular, can be used as biomarker of MS disease severity and progression.
authors.affiliation: Department of Neurology, Baird MS Center, Jacobs Neurological Institute, Buffalo, NY, USA.
authors.forename: Zohara
authors.initials: Z
authors.lastname: Sternberg
authors.affiliation: Department of Neurology, Baird MS Center, Jacobs Neurological Institute, Buffalo, NY, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Chiotti
authors.affiliation: Department of Flow Cytometry, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Tario
authors.affiliation: Department of Neurology, Baird MS Center, Jacobs Neurological Institute, Buffalo, NY, USA.
authors.forename: Trevor
authors.initials: T
authors.lastname: Chichelli
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Neel
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kailash
authors.initials: K
authors.lastname: Chadha
authors.affiliation: Department of Biostatistics, University of Buffalo, Buffalo, NY, USA.
authors.forename: Jinhee
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Neurology, Baird MS Center, Jacobs Neurological Institute, Buffalo, NY, USA.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Karmon
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000737:chemistry; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009103:Multiple Sclerosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D061251:Primary Cell Culture; D011485:Protein Binding; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics*; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood / Q000235:genetics*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology
chemical_list: C000593871:AGER protein, human; D000906:Antibodies; D015415:Biomarkers; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products
keywords: Advanced glycation; Biomarker; Cell surface expression; Disease severity; Flow cytometry; Mononuclear cells