title: Biomarkers of inflammation and axonal degeneration/damage in patients with newly diagnosed multiple sclerosis: contributions of the soluble CD163 CSF/serum ratio to a biomarker panel.
abstract: BACKGROUND
  Expression of soluble CD163 (sCD163), a macrophage/microglia biomarker, is increased in inflammatory conditions, and sCD163 levels in the cerebrospinal fluid (CSF) have recently been shown to be elevated in patients with multiple sclerosis (MS): the sCD163 CSF/serum ratio was elevated in patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and clinically isolated syndrome (CIS) compared with symptomatic controls.
  
  
  OBJECTIVE
  To investigate the contributions of the sCD163 CSF/serum ratio to a biomarker panel focusing on inflammation and axonal degeneration in newly diagnosed MS; thus optimising a diagnostic biomarker panel for MS.
  
  
  METHODS
  After a full MS diagnostic work-up, including collection of paired samples of CSF and serum, 125 patients were included in this study. Patients were divided into groups based on their diagnosis, and patients with normal clinical and paraclinical findings were defined as symptomatic controls. Serum and CSF levels, ratios, and indices of sCD163, CXCL13, osteopontin, neopterin, and CSF levels of neurofilament light polypeptide were determined by enzyme-linked immunosorbent assays (ELISAs). For sCD163 the results constitute a post-hoc analysis of already published data.
  
  
  RESULTS
  All tested biomarkers, notably the sCD163 ratio, the CXCL13 ratio, the NEO ratio, the CSF level of NfL, the IgG index, and the serum level of OPN, were significantly correlated to RRMS, PPMS, and/or CIS. The individual biomarkers in single tests had a lower performance than the IgG index, however, their combined receiver operating characteristic (ROC) curve demonstrated excellent diagnostic discriminatory power.
  
  
  CONCLUSIONS
  The biomarker panel showed distinct profiles for each patient group and could be a valuable tool for clinical differentiation of MS subgroups. The combined ROC analysis showed that sCD163 contributes positively as a diagnostic marker to a panel of established MS biomarkers. Patients with PPMS were demonstrated to have significantly elevated levels of both inflammatory and degenerative markers.
authors: Department of Neurology, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark; Department of Biomedicine, Bartholin Building, Wilhelm Meyers Allé 4, Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Morten
authors: M
authors: Stilund
authors: Department of Biomedicine, Bartholin Building, Wilhelm Meyers Allé 4, Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Mikkel Carstensen
authors: MC
authors: Gjelstrup
authors: Department of Neurology, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark.
authors: Thor
authors: T
authors: Petersen
authors: Department of Clinical Biochemistry, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark.
authors: Holger Jon
authors: HJ
authors: Møller
authors: Department of Neurology, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark.
authors: Peter Vestergaard
authors: PV
authors: Rasmussen
authors: Department of Biomedicine, Bartholin Building, Wilhelm Meyers Allé 4, Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Tove
authors: T
authors: Christensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D019540:Area Under Curve; D001369:Axons / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D054382:Chemokine CXCL13 / Q000097:blood / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016014:Linear Models; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid / Q000175:diagnosis; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000175:diagnosis; D019798:Neopterin / Q000097:blood / Q000134:cerebrospinal fluid; D053495:Osteopontin / Q000097:blood / Q000134:cerebrospinal fluid; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000097:blood; D055815:Young Adult; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D054382:Chemokine CXCL13; D011956:Receptors, Cell Surface; D053495:Osteopontin; D019798:Neopterin