Summary
The presence of free light chains (FLC) was investigated in 32 patients with clinically definite or laboratory supported definite multiple sclerosis (MS), 2 patients with neurosyphilis and 10 normal controls. The detection of FLC in unconcentrated cerebrospinal fluid (CSF) was performed by means of agarose isoelectric focusing, followed by transfer of proteins to nitrocellulose membranes, double immunofixation, avidin-biotin amplification and peroxidase staining. Bands due to FLC were clearly demonstrated in the CSF of 28 MS patients; 3 of them showed only kappa FLC, 10 only lambda FLC, while 15 had both kappa and lambda FLC. The CSF of 4 MS patients was FLC negative. In both cases of neurosyphilis FLC bands were observed. FLC were never found in normal CSF. Among the indexes of intrathecal immunological activity (IgG oligoclonal bands, FLC, IgG index, intra-blood-brain barrier IgG synthesis rate, pleocytosis) the FLC proved to be the second most frequent abnormality in MS CSF, the presence of IgG oligoclonal bands being the first. In one MS case an FLC band was found, while all the other indexes of intrathecal IgG production were negative. A high correlation was found between an elevated number of FLC and pleocytosis. The presence of FLC in MS CSF seems to indicate a recent immunological stimulation leading to increased synthesis of FLC within the CNS.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bergenbrant S, Gallo P, Gudmundsson C, Sidén Å (1986) Two-dimensional gel electrophoresis of cerebrospinal fluid with and without oligoclonal immunoglobulin bands. In: Galteau MM, Siest G (eds) Recent progress in two-dimensional electrophoresis. Presses Universitaires de Nancy, pp 241–244
Bollengier F, Rabinovitch N, Lowenthal A (1978) Oligoclonal immunoglobulins, light chain ratios and free light chains in cerebrospinal fluid and serum from patients affected with various neurological diseases. J Clin Chem Biochem 16:165–173
Gallo P, Bracco F, Battistin L, Tavolato B (1985) Detection of IgG oligoclonal bands in unconcentrated CSF by means of agarose isoelectric focusing, double immunofixation peroxidase staining and avidin-biotin amplification. Ital J Neurol Sci 6:275–282
Grimaldi LME, Roos RP, Malefski EA, Arnason BGW (1985) Oligoclonal IgA bands in multiple sclerosis and subacute sclerosing panencephalitis. Neurology 35:813–817
Keir G, Walker RWH, Thompson EJ (1982) Oligoclonal immunoglobulin M in cerebrospinal fluid from multiple sclerosis patients. J Neurol Sci 57:281–285
Laurenzi MA, Mavra M, Kam-Hansen S, Link H (1980) Oligoclonal IgG and free light chains in multiple sclerosis demonstrated by thin-layer polyacrylamide gel isoelectric focusing and immunofixation. Ann Neurol 8:241–247
Link H (1967) Immunoglobulin G and low molecular weight proteins in human cerebrospinal fluid. Acta Neurol Scand 43 [Suppl 28]:1–136
Link H, Laurenzi MA (1979) Immunoglobulin class and light chain type of oligoclonal bands in CSF in multiple sclerosis determined by agaraose gel electrophoresis and immunofixation. Ann Neurol 6:107–110
Link H, Tibbling G (1977) Principles of albumin and IgG synthesis in neurological disorders. II. Evaluation of IgG synthesis within the central nervous system in multiple sclerosis. Scand J Clin Lab Invest 37:397–401
Lowenthal A, van Sande M, Karcher D (1960) The differential diagnosis of neurological diseases by fractionating electrophoretically the CSF gamma-globulins. J Neurochem 6:51–56
Mattson DH, Roos RP, Arnason BGW (1981) Comparison of agar gel electrophoresis and isoelectric focusing in multiple sclerosis and subacute sclerosing panencephalitis. Ann Neurol 9:34–41
Olsson JE, Nilsson K (1979) Gamma globulins of CSF and serum in multiple sclerosis: isoelectric focusing on polyacrylamide gel and agar gel electrophoresis. Neurology 29:1383–1391
Olsson T, Kostulas V, Link H (1984) Improved detection of oligoclonal IgG in cerebrospinal fluid by isoelectric focusing in agarose, double-antibody peroxidase labeling, and avidin-biotin amplification. Clin Chem 30:1246–1249
Poser CM, Paty DW, Scheimberg L, McDonald WI, Davis FA, Ebers GC, Johnson KP, Sibley WA, Silberberg DH, Tourtellotte WW (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227–231
Rudick RA, Peter DR, Bidlack JM, Knutson DW (1985) Multiple sclerosis: free light chains in cerebrospinal fluid. Neurology 35:1443–1449
Rudick RA, Jacobs L, Kinkel PR, Kinkel WR (1986) Isolated idiopathic optic neuritis. Analysis of free kappa-light chains in cerebrospinal fluid and correlation with nuclear magnetic resonance findings. Arch Neurol 43:456–458
Thompson EJ, Vakaet A (1985) Free light chains in multiple sclerosis. Prot Biol Fluids 32:215–216
Tibbling G, Link H, Ohman S (1977) Principles of albumin and IgG analysis in neurological disorders. I. Establishment of reference values. Scand J Clin Lab Invest 37:385–390
Tourtellotte WW, Potvin AR, Fleming JO, Murthy KN, Levy J, Syndulko K, Potvin JH (1980) Multiple sclerosis: measurement and validation of central nervous system IgG synthesis rate. Neurology 30:240–244
Vakaet A, Thompson EJ (1985) Free light chains in the cerebrospinal fluid: an indicator of recent immunological stimulation. J Neurol Neurosurg Psychiatry 48:995–998
Walker RWT, Keir G, Thompson EJ (1983) Assessment of cerebrospinal fluid immunoglobulin patterns after isoelectric focusing. J Neurol Sci 58:123–134
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bracco, F., Gallo, P., Menna, R. et al. Free light chains in the CSF in multiple sclerosis. J Neurol 234, 303–307 (1987). https://doi.org/10.1007/BF00314285
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00314285