title: Soluble CD27 Levels in Cerebrospinal Fluid as a Prognostic Biomarker in Clinically Isolated Syndrome.
abstract: There is a growing number of therapies that could be administered after the first symptom of central nervous system demyelination. These drugs can delay multiple sclerosis (MS) diagnosis and slow down future disability. However, treatment of patients with benign course may not be needed; therefore, there is a need for biomarkers to predict long-term prognosis in patients with clinically isolated syndrome (CIS).
  
  
  
  To investigate whether the T-cell activation marker soluble CD27 (sCD27) measured in cerebrospinal fluid of patients at time of a first attack is associated with a subsequent diagnosis of MS and a higher relapse rate.
  
  
  
  This prospective study included 77 patients with CIS between March 2002 and May 2015 in a tertiary referral center for multiple sclerosis, in collaboration with several regional hospitals. Patients with CIS underwent a lumbar puncture and magnetic resonance imaging scan within 6 months after first onset of symptoms.
  
  
  
  Soluble CD27 levels were determined in cerebrospinal fluid using a commercially available enzyme-linked immunosorbent assay. Cox regression analyses was used to calculate univariate and multivariate hazard ratios for MS diagnosis. Association between sCD27 levels and relapse rate was assessed using a negative binomial regression model.
  
  
  
  Among 77 patients with CIS, 50 were female (79.5%), and mean (SD) age was 32.7 (7.4) years. Mean (SD) age in the control individuals was 33.4 (9.5) years, and 20 were female (66.7%).Patients with CIS had higher cerebrospinal fluid sCD27 levels than control individuals (geometric mean, 31.3 U/mL; 95% CI, 24.0-40.9 vs mean, 4.67 U/mL; 95% CI, 2.9-7.5; P < .001). During a mean (SD) follow-up of 54.8 (35.1) months, 39 of 77 patients (50.6%) were diagnosed as having MS. In a model adjusted for magnetic resonance imaging and cerebrospinal fluid measurements, sCD27 levels were associated with a diagnosis of MS (hazard ratio, 2.4 per 100 U/mL increase in sCD27 levels; 95% CI, 1.27-4.53; P = .007). Additionally, patients with MS with high sCD27 levels (median, >31.4 U/mL) at the time of CIS had a 5.5 times higher annualized relapse rate than patients with low sCD27 levels (annualized relapse rate, 0.06 vs 0.33; P = .02).
  
  
  
  Soluble CD27 in cerebrospinal fluid of patients with CIS was associated with MS diagnosis and a high relapse rate. Therefore, sCD27 is an activation molecule directly related to the immunopathology of the disease and is a potential clinical marker to help in treatment decisions after a first attack of suspected MS.
authors.affiliation: Department of Neurology, MS Center ErasMS, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Roos M
authors.initials: RM
authors.lastname: van der Vuurst de Vries
authors.affiliation: Department of Neurology, MS Center ErasMS, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Julia Y
authors.initials: JY
authors.lastname: Mescheriakova
authors.affiliation: Department of Neurology, MS Center ErasMS, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Tessel F
authors.initials: TF
authors.lastname: Runia
authors.affiliation: Department of Neurology, MS Center ErasMS, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Naghmeh
authors.initials: N
authors.lastname: Jafari
authors.affiliation: Department of Neurology, MS Center ErasMS, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Theodora A M
authors.initials: TA
authors.lastname: Siepman
authors.forename: Rogier Q
authors.initials: RQ
authors.lastname: Hintzen
mesh_terms: D000328:Adult; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging; D004185:Disability Evaluation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid; D008279:Magnetic Resonance Imaging; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000134:cerebrospinal fluid*; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7