• This record comes from PubMed

Increased intrathecal high-avidity anti-tau antibodies in patients with multiple sclerosis

. 2011 ; 6 (11) : e27476. [epub] 20111129

Language English Country United States Media print-electronic

Document type Journal Article, Research Support, Non-U.S. Gov't

BACKGROUND: Antibodies against tau protein indicate an interaction between the immune system and the neurocytoskeleton and therefore may reflect axonal injury in multiple sclerosis (MS). METHODOLOGY/PRINCIPAL FINDINGS: The levels and avidities of anti-tau IgG antibodies were measured using ELISA in paired cerebrospinal fluid (CSF) and serum samples obtained from 49 MS patients and 47 controls. Anti-tau antibodies were significantly elevated intrathecally (p<0.0001) in the MS group. The CSF anti-tau antibody levels were lower in MS patients receiving therapy than those without treatment (p<0.05). The avidities of anti-tau antibodies were higher in the CSF than in the serum (MS group p<0.0001; controls p<0.005). Anti-tau avidities in the CSF were elevated in MS patients in comparison with controls (p<0.05), but not in serum. CONCLUSIONS: MS patients have higher levels of intrathecal anti-tau antibodies. Anti-tau antibodies have different avidities in different compartments with the highest values in the CSF of MS patients.

See more in PubMed

McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol. 2007;8:913–919. PubMed

Huizinga R, Linington C, Amor S. Resistance is futile: antineuronal autoimmunity in multiple sclerosis. Trends Immunol. 2008;29:54–60. PubMed

Brettschneider J, Maier M, Arda S, Claus A, Sussmuth SD, et al. Tau protein level in cerebrospinal fluid is increased in patients with early multiple sclerosis. Mult Scler. 2005;11:261–265. PubMed

Semra YK, Seidi OA, Sharief MK. Heightened intrathecal release of axonal cytoskeletal proteins in multiple sclerosis is associated with progressive disease and clinical disability. J Neuroimmunol. 2002;122:132–139. PubMed

Terzi M, Birinci A, Cetinkaya E, Onar MK. Cerebrospinal fluid total tau protein levels in patients with multiple sclerosis. Acta Neurol Scand. 2007;115:325–330. PubMed

Brettschneider J, Petzold A, Junker A, Tumani H. Axonal damage markers in the cerebrospinal fluid of patients with clinically isolated syndrome improve predicting conversion to definite multiple sclerosis. Mult Scler. 2006;12:143–148. PubMed

Niebroj-Dobosz I, Dziewulska D, Janik P. Auto-antibodies against proteins of spinal cord cells in cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS). Folia Neuropathol. 2006;44:191–196. PubMed

Silber E, Semra YK, Gregson NA, Sharief MK. Patients with progressive multiple sclerosis have elevated antibodies to neurofilament subunit. Neurology. 2002;58:1372–1381. PubMed

Fialova L, Bartos A, Soukupova J, Svarcova J, Ridzon P, et al. Synergy of serum and cerebrospinal fluid antibodies against axonal cytoskeletal proteins in patients with different neurological diseases. Folia Biol (Praha) 2009;55:23–26. PubMed

Terryberry JW, Thor G, Peter JB. Autoantibodies in neurodegenerative diseases: antigen-specific frequencies and intrathecal analysis. Neurobiol Aging. 1998;19:205–216. PubMed

Ehling R, Lutterotti A, Wanschitz J, Khalil M, Gneiss C, et al. Increased frequencies of serum antibodies to neurofilament light in patients with primary chronic progressive multiple sclerosis. Mult Scler. 2004;10:601–606. PubMed

Bartos A, Fialova L, Soukupova J, Kukal J, Malbohan I, et al. Antibodies against light neurofilaments in multiple sclerosis patients. Acta Neurol Scand. 2007;116:100–107. PubMed

Bartos A, Fialova L, Soukupova J, Kukal J, Malbohan I, et al. Elevated intrathecal antibodies against the medium neurofilament subunit in multiple sclerosis. J Neurol. 2007;254:20–25. PubMed

Svarcova J, Fialova L, Bartos A, Steinbachova M, Malbohan I. Cerebrospinal fluid antibodies to tubulin are elevated in the patients with multiple sclerosis. Eur J Neurol. 2008;15:1173–1179. PubMed

Cleveland DW, Hwo SY, Kirschner MW. Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin. J Mol Biol. 1977;116:207–225. PubMed

Binder LI, Frankfurter A, Rebhun LI. The distribution of tau in the mammalian central nervous system. J Cell Biol. 1985;101:1371–1378. PubMed PMC

Drubin DG, Kirschner MW. Tau protein function in living cells. J Cell Biol. 1986;103:2739–2746. PubMed PMC

Rosenmann H, Meiner Z, Geylis V, Abramsky O, Steinitz M. 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. 2006;410:90–93. PubMed

Lublin FD, Reingold SC. 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. 1996;46:907–911. PubMed

McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121–127. PubMed

Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444–1452. PubMed

Matheus S, Deparis X, Labeau B, Lelarge J, Morvan J, et al. Discrimination between primary and secondary dengue virus infection by an immunoglobulin G avidity test using a single acute-phase serum sample. J Clin Microbiol. 2005;43:2793–2797. PubMed PMC

Himmler A, Drechsel D, Kirschner MW, Martin DW., Jr Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains. Mol Cell Biol. 1989;9:1381–1388. PubMed PMC

Narita M, Yamada S, Matsuzono Y, Itakura O, Togashi T, et al. Immunoglobulin G avidity testing in serum and cerebrospinal fluid for analysis of measles virus infection. Clin Diagn Lab Immunol. 1996;3:211–215. PubMed PMC

Flori P, Tardy L, Patural H, Bellete B, Varlet MN, et al. Reliability of immunoglobulin G antitoxoplasma avidity test and effects of treatment on avidity indexes of infants and pregnant women. Clin Diagn Lab Immunol. 2004;11:669–674. PubMed PMC

Hedman K, Hietala J, Tiilikainen A, Hartikainen-Sorri AL, Raiha K, et al. Maturation of immunoglobulin G avidity after rubella vaccination studied by an enzyme linked immunosorbent assay (avidity-ELISA) and by haemolysis typing. J Med Virol. 1989;27:293–298. PubMed

Cucnik S, Kveder T, Krizaj I, Rozman B, Bozic B. High avidity anti-beta 2-glycoprotein I antibodies in patients with antiphospholipid syndrome. Ann Rheum Dis. 2004;63:1478–1482. PubMed PMC

Cui Z, Wang HY, Zhao MH. Natural autoantibodies against glomerular basement membrane exist in normal human sera. Kidney Int. 2006;69:894–899. PubMed

Milosevic-Jovcic N, Ciric D, Hajdukovic-Dragojlovic L, Mircetic V. Differences in the relationship of specificity to titre and functional affinity between circulating Ga- and pan-reactive IgM rheumatoid factors in rheumatoid arthritis. Rheumatology (Oxford) 2004;43:1190–1193. PubMed

Villalta D, Romelli PB, Savina C, Bizzaro N, Tozzoli R, et al. Anti-dsDNA antibody avidity determination by a simple reliable ELISA method for SLE diagnosis and monitoring. Lupus. 2003;12:31–36. PubMed

Racke MK. The role of B cells in multiple sclerosis: rationale for B-cell-targeted therapies. Curr Opin Neurol. 2008;21(Suppl 1):S9–S18. PubMed

Rosenmann H, Grigoriadis N, Karussis D, Boimel M, Touloumi O, et al. Tauopathy-like abnormalities and neurologic deficits in mice immunized with neuronal tau protein. Arch Neurol. 2006;63:1459–1467. PubMed

Graus F, Saiz A, Dalmau J. Antibodies and neuronal autoimmune disorders of the CNS. J Neurol. 2010;257:509–517. PubMed

Zamecnik J, Cerny R, Bartos A, Jerabek J, Bojar M. Paraneoplastic opsoclonus-myoclonus syndrome associated with malignant fibrous histiocytoma: neuropathological findings. Cesk Patol. 2004;40:63–67. PubMed

Huizinga R, Heijmans N, Schubert P, Gschmeissner S, t Hart BA, et al. Immunization with neurofilament light protein induces spastic paresis and axonal degeneration in Biozzi ABH mice. J Neuropathol Exp Neurol. 2007;66:295–304. PubMed

Bartos A, Pitha J. Opsoclonus-myoclonus-dysequilibrium syndrome: cytological and immunological dynamics in the serial cerebrospinal fluid in two patients. J Neurol. 2003;250:1420–1425. PubMed

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...