title: Free light chain monomer-dimer patterns in the diagnosis of multiple sclerosis.
abstract: In our search of new biomarkers for multiple sclerosis (MS), we aimed to characterize the immunoglobulin (Ig) free light chains (FLC) in patients' cerebrospinal fluid (CSF) and serum, and to evaluate the diagnostic utility of FLC monomer-dimer patterns for MS. FLC were analyzed by Western blotting and mass spectroscopy. CSF and serum samples were examined for the presence of oligoclonal Ig bands by a conventional laboratory test for MS. Three distinct pathological FLC monomer-dimer patterns, typical of MS but not of other neurological diseases, were revealed. In 31 out 56 MS patients the highly increased CSF levels of κ monomers and dimers were demonstrated. In 18 MS patients, the increased κ-FLC levels were accompanied by highly elevated λ dimers. Five MS cases showed no significant elevation in κ-FLC, but they displayed abnormally high λ dimer levels. The intensity of the immunoreactive FLC bands was measured to account for κ and λ monomer and dimer levels and their ratios in the CSF and serum. Combined usage of different FLC parameters allowed the determination of the appropriate FLC threshold values to diagnose MS. The developed method showed higher sensitivity and specificity (96% and 90%, respectively), as compared to those of the conventional OCB test (82% and 70%, respectively). Our study highlights the role of the differential analysis of monomeric and dimeric κ- and λ-FLC for the precise diagnosis of MS.
authors: Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer, Israel. batiakaplan@gmail.com
authors: Batia
authors: B
authors: Kaplan
authors: Sizilia
authors: S
authors: Golderman
authors: Gilad
authors: G
authors: Yahalom
authors: Regina
authors: R
authors: Yeskaraev
authors: Tamar
authors: T
authors: Ziv
authors: Boris M
authors: BM
authors: Aizenbud
authors: Ben-Ami
authors: BA
authors: Sela
authors: Avi
authors: A
authors: Livneh
mesh_terms: D000595:Amino Acid Sequence; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D015153:Blotting, Western; D003937:Diagnosis, Differential; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000737:chemistry; D007145:Immunoglobulin kappa-Chains / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry; D007146:Immunoglobulin lambda-Chains / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D043025:Oligoclonal Bands / Q000097:blood / Q000134:cerebrospinal fluid; D055503:Protein Multimerization; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D043025:Oligoclonal Bands