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Quantification of Immunoglobulin Free Light Chains in CerebroSpinal Fluid by Nephelometry

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Abstract

Oligoclonal free light chains (FLC) banding has been described in multiple sclerosis (MS) and should be correlated with disease activity. However, discrepancies between studies have been reported because of differences in methods. A new quantitative, rapid, and automated method using nephelometry is now available. Our objective was to investigate the interest of this method for the diagnosis and prognosis of MS. For this purpose, FLC index was determined in paired samples of CSF and serum from consecutive and unselected patients from the same department of neurology. We enrolled 89 patients (33 MS, 15 “possible MS”, and 41 controls) and correlated with IgG index, IgG oligoclonal banding, and clinical MS progression criteria. The main results were (1) FLC kappa index was more sensitive but less specific than IgG index for the diagnosis of MS, (2) two MS patients were negative for oligoclonal banding but exhibited a positive kappa index, (3) no relation between FLC kappa indices, MS clinical criteria, and disease progression was found. In conclusion, FLC kappa index should be considered as a useful complementary test for MS diagnosis. Its pronostic interest remains to be determined on a larger cohort of possible MS patients.

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Abbreviations

FLC:

free light chains; CSF, cerebrospinal fluid; MS, multiple sclerosis; EDSS, expanded disability status scale; Ig, immunoglobulin; MRI, magnetic resonance imaging; CISSMS, clinical isolated syndrome suggestive of MS; IEF, isoelectric focusing; CNS, central nervous system.

References

  1. Tibbling GLH, Ohman S: Principles of albumin and IgG analyses in neurological disorders. I. Establishment of reference values. Scand J Clin Lab Invest 37:385–390, 1977

    PubMed  Google Scholar 

  2. Andersson M, Alvarez-Cermeno J, Bernardi G, Cogato I, Fredman P, Frederiksen J, Fredrikson S, Gallo P, Grimaldi LM, Gronning M: Cerebrospinal fluid in the diagnosis of multiple sclerosis: A consensus report. J Neurol Neurosurg Psychiatry 57:897–902, 1994

    PubMed  Google Scholar 

  3. Laman JD, Thompson EJ, Kappos L: Body fluid markers to monitor multiple sclerosis: The assays and the challenges. Mult Scler 4:266–269, 1998

    Article  PubMed  Google Scholar 

  4. Chofflon M, Juillard C, Juillard P, Gauthier G, Grau GE: Tumor necrosis factor alpha production as a possible predictor of relapse in patients with multiple sclerosis. Eur Cytokine Netw 3:523–531, 1992

    PubMed  Google Scholar 

  5. Flachenecker P, Jung S, Rieckmann P, Toyka KV: sICAM-1 is not a marker for disease activity in the relapse-free interval of multiple sclerosis–-A cross-sectional pilot study. J Neurol 249:1001–1003, 2002

    Article  PubMed  Google Scholar 

  6. Ohta M, Ohta K, Ma J, Takeuchi J, Saida T, Nishimura M, Itoh N: Clinical and analytical evaluation of an enzyme immunoassay for myelin basic protein in cerebrospinal fluid. Clin Chem 46:1326–1330, 2000

    PubMed  Google Scholar 

  7. Giovannoni G, Lai M, Kidd D, Thorpe JW, Miller DH, Thompson AJ, Keir G, Feldmann M, Thompson EJ: Daily urinary neopterin excretion as an immunological marker of disease activity in multiple sclerosis. Brain 120:1–13, 1997

    Article  PubMed  Google Scholar 

  8. Goffette S, Schluep M, Henry H, Duprez T, Sindic CJ: Detection of oligoclonal free kappa chains in the absence of oligoclonal IgG in the CSF of patients with suspected multiple sclerosis. J Neurol Neurosurg Psychiatry 75:308–310, 2004

    Article  PubMed  Google Scholar 

  9. Contini C, Fainardi E, Cultrera R, Seraceni S, Castellazzi M, Peyron F, Granieri E: Evidence of cerebrospinal fluid free kappa light chains in AIDS patients with Toxoplasma gondii encephalitis. J Neuroimmunol 108:221–226, 2000

    Article  PubMed  Google Scholar 

  10. Krakauer M, Schaldemose Nielsen H, Jensen J, Sellebjerg F: Intrathecal synthesis of free immunoglobulin light chains in multiple sclerosis. Acta Neurol Scand 98:161–165, 1998

    PubMed  Google Scholar 

  11. Bracco F, Gallo P, Menna R: Routine detection of IgG oligoclonal bands and free light chains patterns by means of agarose isoelectric focusing and avidin-biotin-peroxidase complex staining in multiple sclerosis unconcentrated cerebrospinal fluid. Ital J Neurol Sci 6:81–84, 1987

    PubMed  Google Scholar 

  12. Sindic CJ, Laterre EC: Oligoclonal free kappa and lambda bands in the cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. An immunoaffinity-mediated capillary blot study. J Neuroimmunol 33:63–72, 1991

    Article  PubMed  Google Scholar 

  13. Lamers KJ, de Jong JG, Jongen PJ, Kock-Jansen MJ, Teunesen MA, Prudon-Rosmulder EM: Cerebrospinal fluid free kappa light chains versus IgG findings in neurological disorders: Qualitative and quantitative measurements. J Neuroimmunol 62:19–25, 1995

    Article  PubMed  Google Scholar 

  14. Lolli F, Amaducci L: Measurement of free kappa immunoglobulin light chains in the cerebrospinal fluid by a competitive avidin-biotin ELISA. Clin Chim Acta 182:229–234, 1989

    Article  PubMed  Google Scholar 

  15. Fagnart OC, Sindic CJ, Laterre C: Free kappa and lambda light chain levels in the cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. J Neuroimmunol 19:119–132, 1988

    Article  PubMed  Google Scholar 

  16. Rudick RA, Medendorp SV, Namey M, Boyle S, Fischer J: Multiple sclerosis progression in a natural history study: Predictive value of cerebrospinal fluid free kappa light chains. Mult Scler 1:150–155, 1995

    PubMed  Google Scholar 

  17. Bracco F, Gallo P, Menna R, Battistin L, Tavolato B: Free light chains in the CSF in multiple sclerosis. J Neurol 234:303–307, 1987

    Article  PubMed  Google Scholar 

  18. Vakaet A, Thompson EJ: Free light chains in the cerebrospinal fluid: An indicator of recent immunological stimulation. J Neurol Neurosurg Psychiatry 48:995–998, 1985

    PubMed  Google Scholar 

  19. Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, Drew R: Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 47:673–680, 2001

    PubMed  Google Scholar 

  20. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS: Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127, 2001

    Article  PubMed  Google Scholar 

  21. Barkhof F, Filippi M, Miller DH, Scheltens P, Campi A, Polman CH, Comi G, Ader HJ, Losseff N, Valk J: Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 120:2059–2069, 1997

    Article  PubMed  Google Scholar 

  22. Barkhof F, Rocca M, Francis G, Van Waesberghe JH, Uitdehaag BM, Hommes OR, Hartung HP, Durelli L, Edan G, Fernandez O, Seeldrayers P, Sorensen P, Margrie S, Rovaris M, Comi G, Filippi M: Validation of diagnostic magnetic resonance imaging criteria for multiple sclerosis and response to interferon beta1a. Ann Neurol 53:718–724, 2003

    Article  PubMed  Google Scholar 

  23. Kurtzke JF: Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology 33:1444–1452, 1983

    PubMed  Google Scholar 

  24. Stendahl-Brodin L, Link H: Relation between benign course of multiple sclerosis and low-grade humoral immune response in cerebrospinal fluid. J Neurol Neurosurg Psychiatry 43:102–105, 1980

    PubMed  Google Scholar 

  25. Reiber H, Felgenhauer K: Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system. Clin Chim Acta 163:319–328, 1987

    Article  PubMed  Google Scholar 

  26. Desplat S, Pelletier J, Pouget J, Bellon F, Bernard D, Boucraut J: Sensitized immunofixation: a new technique for analyzing the oligoclonal pattern of CSF immunoglobulins. Rev Neurol 156:885–889, 2000

    PubMed  Google Scholar 

  27. Caudie C, Allausen O, Bancel J: Detection of oligoclonal IgG bands in cerebrospinal fluid by immunofixation after electrophoretic migration in the automated Hydrasys sebia system. Ann Biol Clin 58:376–379, 2000

    Google Scholar 

  28. Richard S, Miossec V, Moreau JF, Taupin JL: Detection of oligoclonal immunoglobulins in cerebrospinal fluid by an immunofixation-peroxidase method. Clin Chem 48:167–173, 2002

    PubMed  Google Scholar 

  29. Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA: Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: Relative sensitivity for detection of monoclonal light chains. Clin Chem 48:1437–1444, 2002

    PubMed  Google Scholar 

  30. Jenkins MA, Cheng L, Ratnaike S: Multiple sclerosis: Use of light-chain typing to assist diagnosis. Ann Clin Biochem 38:235–241, 2001

    Article  PubMed  Google Scholar 

  31. Rudick RA, Pallant A, Bidlack JM, Herndon RM: Free kappa light chains in multiple sclerosis spinal fluid. Ann Neurol 20:63–69,1986

    Article  PubMed  Google Scholar 

  32. Wakasugi K, Suzuki H, Imai A, Konishi S, Kishioka H: Immunoglobulin free light chain assay using latex agglutination. Int J Clin Lab Res 25:211–215, 1995

    PubMed  Google Scholar 

  33. Lolli F, Siracusa G, Amato MP, Fratiglioni L, Dal Pozzo G, Galli E, Amaducci L: Intrathecal synthesis of free immunoglobulin light chains and IgM in initial multiple sclerosis. Acta Neurol Scand 83:239–243, 1991

    PubMed  Google Scholar 

  34. Khoury SJ, Weiner HL: Kappa light chains in spinal fluid for diagnosing multiple sclerosis. JAMA 272:242–243, 1994

    Article  PubMed  Google Scholar 

  35. DeCarli C, Menegus MA, Rudick RA: Free light chains in multiple sclerosis and infections of the CNS. Neurology 37:1334–1338,1987

    PubMed  Google Scholar 

  36. Fischer C, Arneth B, Koehler J, Lotz J, Lackner KJ: Kappa free light chains in cerebrospinal fluid as markers of intrathecal immunoglobulin synthesis. Clin Chem 50:1809–1813, 2004

    Article  PubMed  Google Scholar 

  37. Leary SM, McLean BN, Thompson EJ: Local synthesis of IgA in the cerebrospinal fluid of patients with neurological diseases. J Neurol 247:609–615, 2000

    Article  PubMed  Google Scholar 

  38. Rudick RA, Cookfair DL, Simonian NA, Ransohoff RM, Richert JR, Jacobs LD, Herndon RM, Salazar AM, Fischer JS, Granger CV, Goodkin DE, Simon JH, Bartoszak DM, Bourdette DN, Braiman J, Brownscheidle CM, Coats ME, Cohan SL, Dougherty DS, Kinkel RP, Mass MK, Munchsauer FE, O’Reilly K, Priore RL, Whitham RH: Cerebrospinal fluid abnormalities in a phase III trial of Avonex (IFNbeta-1a) for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group. J Neuroimmunol 93:8–14,1999

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratoire d’Immunologie, Hôpital de la Conception, 147, Bd Baille, 13005 Marseille/UMR 6184, Faculté de Médecine Timone, 27, Bd Jean Moulin, 13005, Marseille, France

    Sophie Desplat-jégo, Dominique Bernard & José Boucraut

  2. Service de Neurologie, Hôpital de la Timone, Bd Jean Moulin, 13005, Marseille, France

    Lionel Feuillet, Jean Pelletier & André Ali Chérif

  3. UMR 6184, Faculté de Médecine Timone, 27, Bd Jean Moulin, 13005, Marseille, France

    José Boucraut

Authors
  1. Sophie Desplat-jégo
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  2. Lionel Feuillet
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  3. Jean Pelletier
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  4. Dominique Bernard
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  5. André Ali Chérif
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  6. José Boucraut
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Correspondence to José Boucraut.

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Desplat-jégo, S., Feuillet, L., Pelletier, J. et al. Quantification of Immunoglobulin Free Light Chains in CerebroSpinal Fluid by Nephelometry. J Clin Immunol 25, 338–345 (2005). https://doi.org/10.1007/s10875-005-5371-9

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  • DOI: https://doi.org/10.1007/s10875-005-5371-9

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