title: Diagnostic and Prognostic Value of the Cerebrospinal Fluid Concentration of Immunoglobulin Free Light Chains in Clinically Isolated Syndrome with Conversion to Multiple Sclerosis.
abstract: OBJECTIVE
  In this study, we evaluated the diagnostic and prognostic significance of cerebrospinal fluid free light chains (CSF FLC) at the time of clinically isolated syndrome (CIS).
  
  
  METHODS
  We compared FLC-parameters at the moment of CIS in patients with conversion to multiple sclerosis (MS) after 2 years (CIS-MS), patients who remained stable both clinically and radiologically after 2 years (CIS-nonMS), patients with non-inflammatory neurologic diseases (NIND) as a comparison group and patients with other inflammatory neurologic diseases (IND) with intrathecal oligoclonal bands (OCB) synthesis. ROC-analysis was conducted to define FLC-assay characteristics and cut-off values. We also compared FLC-concentrations in CIS patients to determine their OCB-status. A correlation analysis was performed between FLC-concentrations and the expanded disability scale score (EDSS), annualized relapse rate (ARR) and MRI-activity (i.e., number of new and gadolinium-enhancing (Gd+) lesions) in patients.
  
  
  RESULTS
  The levels of kappa-FLC (k-FLCCSF) and lambda-FLC (λ-FLCCSF) as well as kappa- and lambda-quotients (Q-k and Q-λ) were elevated in CIS-MS compared to the CIS-nonMS and NIND groups. These levels did not differ significantly when compared with the IND group. We identified several patients with high k-FLCCSF and λ-FLCCSF in OCB-negative CIS and IND groups. The level of k-FLCCSF production was significantly higher in OCB-positive patients in the CIS-MS group compared to the CIS-nonMS group. The concentrations of k-FLCCSF and Q-k in the CIS-MS group showed significant correlation with the level of EDSS after 2 years (k-FLC: r = 0.4477,p = 0.0016; Q-k: r = 0.4621, p = 0.0016). λ-FLCCSF and Q-λ inversely correlated with the number of Gd+ lesions (CSF λ-FLC: r = -0.3698, p = 0.0223; Q-λ: r = -0.4527, p = 0.0056).
  
  
  CONCLUSIONS
  The concentration of CSF FLC predicts conversion to MS within 2 years following CIS. OCB-positive patients with an early conversion have a higher concentration of CSF-FLC. We have also shown a prognostic significance of k-FLCCSF for future EDSS-progression.
authors.affiliation: Municipal Clinical Hospital No 31, City Center of Multiple Sclerosis and Autoimmune Diseases, Saint-Petersburg, Russian Federation.
authors.forename: Gleb
authors.initials: G
authors.lastname: Makshakov
authors.affiliation: First Pavlov State Saint-Petersburg Medical University, Center for Molecular Medicine, Laboratory of Autoimmune diagnostics, Saint-Petersburg, Russian Federation.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Nazarov
authors.affiliation: Municipal Clinical Hospital No 31, City Center of Multiple Sclerosis and Autoimmune Diseases, Saint-Petersburg, Russian Federation.
authors.forename: Olga
authors.initials: O
authors.lastname: Kochetova
authors.affiliation: First Pavlov State Saint-Petersburg Medical University, Center for Molecular Medicine, Laboratory of Autoimmune diagnostics, Saint-Petersburg, Russian Federation.
authors.forename: Elena
authors.initials: E
authors.lastname: Surkova
authors.affiliation: First Pavlov State Saint-Petersburg Medical University, Center for Molecular Medicine, Laboratory of Autoimmune diagnostics, Saint-Petersburg, Russian Federation.
authors.forename: Sergey
authors.initials: S
authors.lastname: Lapin
authors.affiliation: Municipal Clinical Hospital No 31, City Center of Multiple Sclerosis and Autoimmune Diseases, Saint-Petersburg, Russian Federation.
authors.forename: Evgeniy
authors.initials: E
authors.lastname: Evdoshenko
mesh_terms: D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000134:cerebrospinal fluid* / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000134:cerebrospinal fluid; D007146:Immunoglobulin lambda-Chains / Q000134:cerebrospinal fluid; D008297:Male; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000276:immunology; D011379:Prognosis; D012372:ROC Curve; D055815:Young Adult
chemical_list: D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains