Folia Microbiologica

, Volume 57, Issue 5, pp 415–419 | Cite as

Avidity of anti-neurocytoskeletal antibodies in cerebrospinal fluid and serum

  • L. Fialová
  • J. Švarcová
  • A. Bartos
  • I. Malbohan


Antibodies have different avidities that can be evaluated using modified enzyme-linked immunosorbent assay (ELISA) techniques. We determined levels and avidities of antibodies to light (NFL) and medium (NFM) subunits of neurofilaments and tau protein in serum and cerebrospinal fluid (CSF) from 26 patients and anti-tau antibody levels and their avidities in 20 multiple sclerosis (MS) patients and 20 age- and sex-matched controls. Each sample was analyzed using both standard ELISA and also using a similar ELISA protocol with the addition of urea. The avidities of anti-neurocytoskeletal antibodies were higher in the CSF than those in serum (anti-NFL, p < 0.0001; anti-tau, p < 0.01; anti-NFM, n.s.). There was no relationship between avidities in serum and CSF for individual anti-neurocytoskeletal antibodies. We did not observe the relationship among the avidities of various anti-neurocytoskeletal antibodies. The avidities of anti-tau antibodies in the CSF were significantly higher in the MS patients than those in the controls (p < 0.0001). The study demonstrates the differences in avidities of CSF or serum neurocytoskeletal antibodies measured as the urea resistance by ELISA method. Avidity determination of anti-neurocytoskeletal antibodies could contribute to the evaluation of the immunological status of patients.


Multiple Sclerosis Multiple Sclerosis Patient Expand Disability Status Scale Glatiramer Urea Solution 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Bovine serum albumin


Cerebrospinal fluid


Enzyme-linked immunosorbent assay




Multiple sclerosis


The light subunit of neurofilament


Medium subunit of neurofilament


Not significant


Phosphate-buffered saline


Spearman’s correlation coefficient



The study was supported by a grant from the Ministry of Health No NS 10369-3.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Avrameas S, Ternynck T (1993) The natural autoantibodies system: between hypotheses and facts. Mol Immunol 30:1133–1142PubMedCrossRefGoogle Scholar
  2. Bartos A, Fialova L, Soukupova J, Kukal J, Malbohan I, Pit'ha J (2007a) Elevated intrathecal antibodies against the medium neurofilament subunit in multiple sclerosis. J Neurol 254:20–25PubMedCrossRefGoogle Scholar
  3. Bartos A, Fialova L, Soukupova J, Kukal J, Malbohan I, Pitha J (2007b) Antibodies against light neurofilaments in multiple sclerosis patients. Acta Neurol Scand 116:100–107PubMedCrossRefGoogle Scholar
  4. Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I, Dilitz E, Deisenhammer F, Reindl M (2003) Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 349:139–145PubMedCrossRefGoogle Scholar
  5. Cui Z, Zhao MH (2005) Avidity of anti-glomerular basement membrane autoantibodies was associated with disease severity. Clin Immunol 116:77–82PubMedCrossRefGoogle Scholar
  6. de Souza VA, Pannuti CS, Sumita LM, de Andrade Junior HF (1997) Enzyme-linked immunosorbent assay-IgG antibody avidity test for single sample serologic evaluation of measles vaccines. J Med Virol 52:275–279PubMedCrossRefGoogle Scholar
  7. Fialova L, Bartos A, Soukupova J, Svarcova J, Ridzon P, Malbohan I (2009) Synergy of serum and cerebrospinal fluid antibodies against axonal cytoskeletal proteins in patients with different neurological diseases. Folia Biol (Praha) 55:23–26Google Scholar
  8. Flori P, Tardy L, Patural H, Bellete B, Varlet MN, Hafid J, Raberin H, Sung RT (2004) Reliability of immunoglobulin G antitoxoplasma avidity test and effects of treatment on avidity indexes of infants and pregnant women. Clin Diagn Lab Immunol 11:669–674PubMedGoogle Scholar
  9. Giovannoni G, Chapman MD, Thompson EJ (2006) The role of antibody affinity for specific antigens in the differential diagnosis of inflammatory nervous system disorders. J Neuroimmunol 180:29–32PubMedCrossRefGoogle Scholar
  10. Huizinga R, Heijmans N, Schubert P, Gschmeissner S, t Hart BA, Herrmann H, Amor S (2007) Immunization with neurofilament light protein induces spastic paresis and axonal degeneration in Biozzi ABH mice. J Neuropathol Exp Neurol 66:295–304PubMedCrossRefGoogle Scholar
  11. Ilyas AA, Chen ZW, Cook SD (2003) Antibodies to sulfatide in cerebrospinal fluid of patients with multiple sclerosis. J Neuroimmunol 139:76–80PubMedCrossRefGoogle Scholar
  12. Jianping L, Zhibing Y, Wei Q, Zhikai C, Jie X, Jinbiao L (2006) Low avidity and level of serum anti-Abeta antibodies in Alzheimer disease. Alzheimer Dis Assoc Disord 20:127–132PubMedCrossRefGoogle Scholar
  13. Jimenez-Jimenez FJ, Hernanz A, Medina-Acebron S, de Bustos F, Zurdo JM, Alonso H, Puertas I, Barcenilla B, Sayed Y, Cabrera-Valdivia F (2005) Tau protein concentrations in cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Acta Neurol Scand 111:114–117PubMedCrossRefGoogle Scholar
  14. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452PubMedCrossRefGoogle Scholar
  15. Lim ET, Sellebjerg F, Jensen CV, Altmann DR, Grant D, Keir G, Thompson EJ, Giovannoni G (2005) Acute axonal damage predicts clinical outcome in patients with multiple sclerosis. Mult Scler 11:532–536PubMedCrossRefGoogle Scholar
  16. Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46:907–911PubMedCrossRefGoogle Scholar
  17. Martinez-Yelamos A, Saiz A, Bas J, Hernandez JJ, Graus F, Arbizu T (2004) Tau protein in cerebrospinal fluid: a possible marker of poor outcome in patients with early relapsing-remitting multiple sclerosis. Neurosci Lett 363:14–17PubMedCrossRefGoogle Scholar
  18. Matheus S, Deparis X, Labeau B, Lelarge J, Morvan J, Dussart P (2005a) Discrimination between primary and secondary dengue virus infection by an immunoglobulin G avidity test using a single acute-phase serum sample. J Clin Microbiol 43:2793–2797PubMedCrossRefGoogle Scholar
  19. Matheus S, Deparis X, Labeau B, Lelarge J, Morvan J, Dussart P (2005b) Use of four dengue virus antigens for determination of dengue immune status by enzyme-linked immunosorbent assay of immunoglobulin G avidity. J Clin Microbiol 43:5784–5786PubMedCrossRefGoogle 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 (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127PubMedCrossRefGoogle Scholar
  21. Narita M, Yamada S, Matsuzono Y, Itakura O, Togashi T, Kikuta H (1996) Immunoglobulin G avidity testing in serum and cerebrospinal fluid for analysis of measles virus infection. Clin Diagn Lab Immunol 3:211–215PubMedGoogle Scholar
  22. Poser CM, Paty DW, Scheinberg 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 13:227–231PubMedCrossRefGoogle Scholar
  23. Rosenmann H, Meiner Z, Geylis V, Abramsky O, Steinitz M (2006) Detection of circulating antibodies against tau protein in its unphosphorylated and in its neurofibrillary tangles-related phosphorylated state in Alzheimer's disease and healthy subjects. Neurosci Lett 410:90–93PubMedCrossRefGoogle Scholar
  24. Silber E, Semra YK, Gregson NA, Sharief MK (2002) Patients with progressive multiple sclerosis have elevated antibodies to neurofilament subunit. Neurology 58:1372–1381PubMedCrossRefGoogle Scholar
  25. Skoda D, Kranda K, Bojar M, Glosova L, Baurle J, Kenney J, Romportl D, Pelichovska M, Cvachovec K (2006) Antibody formation against beta-tubulin class III in response to brain trauma. Brain Res Bull 68:213–216PubMedCrossRefGoogle Scholar
  26. Sussmuth SD, Reiber H, Tumani H (2001) Tau protein in cerebrospinal fluid (CSF): a blood–CSF barrier related evaluation in patients with various neurological diseases. Neurosci Lett 300:95–98PubMedCrossRefGoogle Scholar
  27. Svarcova J, Fialova L, Bartos A, Steinbachova M, Malbohan I (2008) Cerebrospinal fluid antibodies to tubulin are elevated in the patients with multiple sclerosis. Eur J Neurol 15:1173–1179PubMedCrossRefGoogle Scholar
  28. Vyshkina T, Kalman B (2008) Autoantibodies and neurodegeneration in multiple sclerosis. Lab Invest 88:796–807PubMedCrossRefGoogle Scholar
  29. Zaffaroni M (2003) Biological indicators of the neurodegenerative phase of multiple sclerosis. Neurol Sci 24(Suppl 5):S279–282PubMedCrossRefGoogle Scholar
  30. Zetterberg H, Jacobsson J, Rosengren L, Blennow K, Andersen PM (2007) Cerebrospinal fluid neurofilament light levels in amyotrophic lateral sclerosis: impact of SOD1 genotype. Eur J Neurol 14:1329–1333PubMedCrossRefGoogle Scholar

Copyright information

© Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i. 2012

Authors and Affiliations

  • L. Fialová
    • 1
  • J. Švarcová
    • 1
  • A. Bartos
    • 2
    • 3
  • I. Malbohan
    • 1
  1. 1.First Faculty of Medicine and General University Hospital, Institute of Medical Biochemistry and Laboratory DiagnosticsCharles University in PraguePrague 2Czech Republic
  2. 2.Prague Psychiatric CenterBohniceCzech Republic
  3. 3.Third Faculty of Medicine, University Hospital Královské Vinohrady, Department of NeurologyCharles University in PraguePrague 10Czech Republic

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