title: Interleukin-12p40 in the spinal fluid as a biomarker for clinically isolated syndrome.
abstract: BACKGROUND
  The cerebrospinal (CSF) constitutes a specific immune micro-environment to the central nervous system, thus it may contain specific biomarkers involved in the pathogenesis of multiple sclerosis (MS).
  
  
  OBJECTIVE
  We aimed to study a large array of inflammatory CSF biomarkers in patients with suspected MS to recognize potential early diagnostic markers.
  
  
  METHODS
  CSF samples were obtained from 115 patients who presented with neurological symptomatology suggestive of MS as follows: clinically isolated syndrome (CIS) = 49, relapsing-remitting multiple sclerosis (RRMS) = 29, and other neurologic disorders (OND) = 37. Protein expression profiles of 30 inflammatory biomarkers were measured by multiplex Luminex bead assay and further analyzed by group comparison statistics, correlation studies and receiver-operating characteristic (ROC) analysis.
  
  
  RESULTS
  Interleukin-12 subunit p40 (IL12p40) demonstrated a significant differential expression pattern between the groups (CIS vs OND: p = 1.17*10(-7); RRMS vs OND: p = 4.98*10(-5)), with higher levels in CIS and RRMS patients. ROC analysis demonstrated excellent diagnostic performance of IL12p40 for discrimination between CIS and OND patients (area under the curve = 0.87 (95% CI 0.78-0.93), p = 0.0001). No associations were found with disease activity or severity measures.
  
  
  CONCLUSIONS
  An increased IL12p40 level characterizes the CSF of MS patients and appears to be helpful in identifying CIS and OND patients early in the process of clinical diagnostic assessment.
authors.affiliation: Multiple Sclerosis Center, Sheba Medical Center, Israel.
authors.forename: Rotem
authors.initials: R
authors.lastname: Orbach
authors.forename: Michael
authors.initials: M
authors.lastname: Gurevich
authors.forename: Anat
authors.initials: A
authors.lastname: Achiron
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002493:Central Nervous System Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid; D012372:ROC Curve; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053762:Interleukin-12 Subunit p40
keywords: Multiple sclerosis; biological markers; cerebrospinal fluid; clinically isolated syndrome; immunology; interleukin-12 subunit p40