title: Prognostic value of free light chains lambda and kappa in early multiple sclerosis.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) have been suggested as quantitative alternative to oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS). However, little is known on their role in predicting clinical and paraclinical disease progression, particularly in early stages.
  
  
  OBJECTIVE
  To assess the prognostic value of FLC in OCB-positive patients with clinically isolated syndrome (CIS) suggestive of MS and early MS.
  
  
  METHODS
  We determined FLC kappa (KFLC) and lambda (LFLC) in CSF and serum by nephelometry in 61 patients (CIS ( n = 48), relapsing-remitting multiple sclerosis ( n = 13)) and 60 non-inflammatory neurological controls. Median clinical follow-up time in CIS was 4.8 years (interquartile range (IQR), 1.5-6.5 years). Patients underwent 3T magnetic resonance imaging (MRI) at baseline and follow-up (median time interval, 2.2 years; IQR, 1.0-3.7 years) to determine T2 lesion load (T2LL) and percent brain volume change (PBVC).
  
  
  RESULTS
  CSF FLC were significantly increased in CIS/MS compared to controls (all p < 0.001). A lower KFLC/LFLC CSF ratio was associated with CIS-clinically definite multiple sclerosis (CDMS) conversion (hazard ratio (HR) = 2.89; 95% confidence interval (CI) = 1.17-7.14; p < 0.05). No correlations were found for FLC variables with T2LL or PBVC.
  
  
  CONCLUSIONS
  Our study confirms increased intrathecal synthesis of FLC in CIS/MS which supports their diagnostic contribution. The KFLC/LFLC CSF ratio appears to have a prognostic value in CIS beyond OCB.
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Margarete M
authors.initials: MM
authors.lastname: Voortman
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stojakovic
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Pirpamer
authors.affiliation: Division of Neuroradiology, Vascular and Interventional Radiology, Medical University of Graz, Graz, Austria.
authors.forename: Margit
authors.initials: M
authors.lastname: Jehna
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Langkammer
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ropele
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Seifert-Held
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Juan-Jose
authors.initials: JJ
authors.lastname: Archelos
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Siegrid
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria/Division of Neuroradiology, Vascular and Interventional Radiology, Medical University of Graz, Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Enzinger
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Khalil
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000097:blood / Q000134:cerebrospinal fluid*; D007146:Immunoglobulin lambda-Chains / Q000097:blood / Q000134:cerebrospinal fluid*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging; D011379:Prognosis
chemical_list: D015415:Biomarkers; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains
keywords: Multiple sclerosis; cerebrospinal fluid; immunoglobulin kappa chains; immunoglobulin lambda chains; magnetic resonance imaging; prognosis; serum