Detection of oligoclonal IgG kappa and IgG lambda bands in cerebrospinal fluid and serum with Hevylite™ antibodies. comparison with the free light chain oligoclonal pattern

Fluids and Barriers of the CNS

Olga Zapletalová²  Ivana Woznicová²  Eva Mojžíšková²  Zdeněk Švagera¹  Pavel Hradílek²  David Zeman² 

[1] Institute of Clinical Biochemistry, University Hospital Ostrava, 17. Listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic;Clinic of Neurology, University Hospital Ostrava, 17. Listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic

关键词: Hevylite™;    Free light chains;    IgG lambda;    IgG kappa;    Oligoclonal bands;    Cerebrospinal fluid;   

Others  :  807359
DOI  :  10.1186/2045-8118-9-5

 received in 2011-10-20, accepted in 2012-02-23,  发布年份 2012

【 摘 要 】

Background

Oligoclonal IgG bands in cerebrospinal fluid that are absent in serum indicate intrathecal IgG synthesis and are a sensitive marker of CNS inflammatory diseases, in particular multiple sclerosis. It may be of interest to determine whether these bands are predominantly IgGκ or IgGλ.

Methods

We have used Hevylite™ antibodies and developed a technique for detection of oligoclonal IgGκ and IgGλ bands by means of isoelectric focusing followed by immunoblotting. The same technique was used for oligoclonal free κ and free λ detection. Among several techniques tested, affinity immunoblotting appears to be the most sensitive; it can detect less than 1 ng of IgGκ or IgGλ paraprotein. We compared oligoclonal IgG profiles with those of oligoclonal IgGκ and IgGλ. There was good agreement concerning the presence or absence of intrathecal synthesis. We observed the ratios between oligoclonal IgGκ and IgGλ bands, and they did not always match the ratios between free κ and free λ bands. We were also able to detect antigen-specific CSF-restricted oligoclonal IgGκ and IgGλ bands in neuroborreliosis. It remains to be determined subsequently by a clinically-oriented prospective study, whether predominant IgGκ/IgGλ or free κ/free λ can be observed more frequently in particular diseases with oligoclonal IgG synthesis.

Discussion

Very sensitive detection of oligoclonal IgGκ and IgGλ bands in cerebrospinal fluid with Hevylite antibodies is feasible; detection of antigen-specific IgGκ or IgGλ is possible as well. In particular situations, e.g. when difficulties arise in distinguishing between oligoclonal and monoclonal pattern, the test may be of considerable clinical value.

【 授权许可】

   
2012 Zeman et al; BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Andersson M, Alvarez-Cermeño J, Bernardi G, Cogato I, Fredman P, Frederiksen J, Fredrikson S, Gallo P, Grimaldi LM, Grønning M, Kier G, Lamers K, Link H, Magalhães A, Massaro AR, Öhman S, Reiber H, Rönnbäcks L, Schluep M, Schuller E, Sindic CJM, Thompson EJ, Trojano M, Wurster U: Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry 1994, 57:897-902.
• [2]Freedman MS, Thompson EJ, Deisenhammer F, Giovannoni G, Grimsley G, Keir G, Öhman S, Racke MK, Sharief M, Sindic CJM, Sellebjerg F, Tourtellotte WW: Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis. Arch Neurol 2005, 62:865-870.
• [3]Link H, Huang YM: Oligoclonal bands in multiple sclerosis cerebrospinal fluid: An update on methodology and clinical usefulness. J Neuroimmunol 2006, 180:17-28.
• [4]Link H, Zettervall O: Multiple sclerosis: disturbed kappa:lambda chain ratio of immunoglobulin G in cerebrospinal fluid. Clin Exp Immunol 1970, 6:435-438.
• [5]Roberts-Thomson PJ, Esiri MM, Young AC, Maclennan ICM: Cerebrospinal fluid immunoglobulin quotients, kappa/lambda ratios, and viral antibody titres in neurological disease. J Clin Path 1976, 29:1105-1115.
• [6]Eickhoff K, Heipertz R, Wikström J: Determination of k/l immunoglobulin light chain ratios in CSF from patients with multiple sclerosis and other neurological diseases. Acta Neurol Scand 1978, 57:385-395.
• [7]Eickhoff K: Messung und diagnostische Bedeutung des κ/λ-Quotienten. In Neue Labormethoden für die Liquordiagnostik. Edited by Kleine T. Stuttgart: Thieme; 1980:26-29.
• [8]Laurenzi MA, Link H: Immunoglobulin class and light chain type of oligoclonal bands in CSF in multiple sclerosis determined by agarose gel electrophoresis and immunofixation. Ann Neurol 1979, 6:107-110.
• [9]Kleine TO: Heterogeneous humoral immune responses in cerebrospinal fluid arising from inflammatory diseases of the human central nervous system. Detection of oligoclonal immunoglobulin bands after isoelectric focusing. Anal Chim Acta 1999, 393:83-93.
• [10]Jenkins MA, Cheng L, Ratnaike S: Multiple sclerosis: use of light-chain typing to assist diagnosis. Ann Clin Biochem 2001, 38:235-241.
• [11]Araga S, Kagimoto H, Wada A, Funamoto K, Inoue K, Takahashi K: Kappa/lambda ratios in IgG, IgA and IgM of cerebrospinal fluid and of sera in patients with multiple sclerosis. Autoimmunity 1989, 5:133-137.
• [12]Bradwell AR, Harding SJ, Fourrier NJ, Wallis GLF, Drayson MT, Carr-Smith HD, Mead GP: Assessment of monoclonal gammopathies by nephelometric measurement of individual immunoglobulin κ/λ ratios. Clin Chem 2009, 55(9):1646-1655.
• [13]Bradwell AR: Analysis of immunoglobulin heavy chain/light chain pairs (Hevylite™). In Serum free light chain analysis (plus Hevylite). 6th edition. Edited by Bradwell AR. Birmingham: The Binding Site Group Ltd; 2010:301-320.
• [14]Reiber H: Flow rate of cerebrospinal fluid (CSF) - a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci 1994, 122:189-203.
• [15]Reiber H, Kruse-Sauter L: for the German Society for CSF diagnostics and clinical neurochemistry, DGLN. [http://www.uke.de/extern/dgln/] webciteInterpretation der Bandenmuster von oligoklonalem IgG in Liquor und Serum
• [16]Knisley KA, Rodkey LS: Affinity immunoblotting. High resolution isoelectric focusing analysis of antibody clonotype distribution. J Immunol Methods 1986, 95:79-87.
• [17]Kaiser R: Affinity immunoblotting: rapid and sensitive detection of oligoclonal IgG, IgA and IgM in unconcentrated CSF by agarose isoelectric focusing. J Neurol Sci 1991, 103:216-225.
• [18]Sindic CJM, 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 1991, 33:63-72.
• [19]Ikegaki N, Kennett RH: Glutaraldehyde fixation of the primary antibody-antigen complex on nitrocellulose paper increases the overall sensitivity of immunoblot assay. J Immunol Methods 1989, 124:205-210.
• [20]Nováčková L, Zeman D: Detection of oligoclonal IgG bands in cerebrospinal fluid and serum: comparison between commercially available immunofixation method and home-made affinity immunoblotting method and evaluation of interobserver agreement. Klin Biochem Metabol 2011, 19:229-233.
• [21]Zettervall O, Link H: Electrophoretic distribution of kappa and lambda immunoglobulin light chain determinants in serum and cerebrospinal fluid in multiple sclerosis. Clin Exp Immunol 1970, 7:365-372.
• [22]Gallo P, Visentini E, Tavolato B: Study of the IgG oligoclonal bands in cerebral spinal fluid in multiple sclerosis by electroimmunofixation. It J Neurol Sci 1982, 3:311-315.
• [23]Gofette S, Schluep M, Henry H, Duprez T, Sindic CJM: 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 2004, 75:308-310.
• [24]DeCarli C, Menegus MA, Rudick RA: Free light chains in multiple sclerosis and infections of the CNS. Neurology 1987, 37:1334-1338.
• [25]Fagnart OC, Sindic CJM, Laterre C: Free kappa and lambda light chain levels in the cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. J Neuroimmunol 1988, 19:119-132.
• [26]Lolli F, Amaducci L: Measurement of free kappa immunoglobulin light chains in the cerebrospinal fluid by a competitive avidin-biotin ELISA. Clin Chim Acta 1989, 182:229-234.
• [27]Totolyan NA, Gryazeva IV, Klimovich VB, Skoromets AA: [Content of free light chains of cerebrospinal fluid immunoglobulins and the importance of its estimation for differential diagnosis of multiple sclerosis]. Zh Nevropatol Psikiatr Im S S Korsakova 1994, 94:49-53.
• [28]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 2004, 50:1809-1813.
• [29]Desplat-Jégo S, Feuillet L, Pelletier J, Bernard D, Ali Chérif A, Boucraut J: Quantification of immunoglobulin free light chains in cerebrospinal fluid by nephelometry. J Clin Immunol 2005, 25:338-345.
• [30]Presslauer S, Milosavljevic D, Brücke T, Bayer P, Hübl W: Elevated levels of kappa free light chains in CSF support the diagnosis of multiple sclerosis. J Neurol 2008, 255:1508-1514.
• [31]Arneth B, Birklein F: High sensitivity of free lambda and free kappa light chains for detection of intrathecal immunoglobulin synthesis in cerebrospinal fluid. Acta Neurol Scand 2009, 119:39-44.
• [32]Kaplan B, Aizenbud BM, Golderman S, Yaskariev R, Sela BA: Free light chain monomers in the diagnosis of multiple sclerosis. J Neuroimmunol 2010, 229:263-271.
• [33]Cotarlu D, Kaufman S, Golik A, Scharf S, Zaldman JL: Heavy- and free light-chain myeloma associated with peripheral polyneuropathy. Clin Chem 1988, 34/12:2594-2595.
• [34]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 2000, 108:221-226.
• [35]Van der Veeken J, Redegeld FA: Immunoglobulin free light chains in immune responses. Current Immunology Reviews 2008, 4:88-100.
• [36]Nakano T, Matsui M, Inoue I, Awata T, Katayama S, Murakoshi T: Free immunoglobulin light chain: Its biology and implications in diseases. Clin Chim Acta 2011, 412:843-849.