| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Department of Neuroimmunology, Guy’s, King’s, and St. Thomas’ School of Medicine, King’s College, London, United Kingdom.
Address correspondence and reprint requests to Dr. Eli Silber, King’s Regional Neurosciences Centre, Mapother House, King’s College Hospital, Denmark Hill, London, SE5 8RS, UK; e-mail: eli.silber{at}kcl.ac.uk
Objective: The cause of axonal loss, an important contributor to disability in MS, is poorly understood. This study investigated whether progression in MS is associated with CSF antibodies to the 68-kd light neurofilament subunit (NF-L), an axonal cytoskeletal protein, and compared this with antibodies against tubulin and the heavy neurofilament subunit (NF-H).
Methods: IgG to NF-L, tubulin, and NF-H was measured by immunoassay in matched CSF and serum samples from patients with relapsing-remitting MS (RRMS; n = 39), primary progressive MS (PPMS; n = 10), and secondary progressive MS (SPMS; n = 18); patients with other inflammatory (n = 21) and noninflammatory (n = 40) neurologic diseases; and healthy controls (n = 12). Immunocytochemistry was performed to assess antibody binding to human brain sections, and isoelectric focusing with immunoblotting was performed to assess oligoclonal anti-NF-L production.
Results: Intrathecal production of anti-NF-L antibodies was significantly elevated in PPMS and SPMS. In contrast, there were no significant differences in CSF levels of antibodies to tubulin or NF-H between the groups. Anti-NF-L, antitubulin, and anti-NF-H levels correlated with the duration of disease before lumbar puncture and Expanded Disability Status Scale levels. Immunocytochemistry demonstrated binding of CSF or serum antibodies to axonal or neuronal components in six of seven RRMS patients, seven of seven PPMS patients, and eight of 10 SPMS patients tested. Isoelectric focusing demonstrated independent CSF oligoclonal bands reactive with NF-L in six of 13 specimens tested.
Conclusions: Anti-NF-L antibodies seem to be raised in progressive MS and may serve as a marker for axonal loss and disease progression. They may contribute to axonal loss and the accumulation of disability.
This article has been cited by other articles:
|
|
 |
|
  R. A. Linker and B. C. Kieseier Review: Innovative monoclonal antibody therapies in multiple sclerosis Therapeutic Advances in Neurological Disorders, July 1, 2008; 1(1): 33 - 42. [Abstract] [PDF]
|
|
|
|
 |
|
 P. H. Lalive, T. Menge, C. Delarasse, B. Della Gaspera, D. Pham-Dinh, P. Villoslada, H.-C. von Büdingen, and C. P. Genain Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis PNAS, February 14, 2006; 103(7): 2280 - 2285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ebringer, L. Hughes, T. Rashid, and C. Wilson Acinetobacter Immune Responses in Multiple Sclerosis: Etiopathogenetic Role and Its Possible Use as a Diagnostic Marker Arch Neurol, January 1, 2005; 62(1): 33 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Ehling, A Lutterotti, J Wanschitz, M Khalil, C Gneiss, F Deisenhammer, M Reindl, and T Berger Increased frequencies of serum antibodies to neurofilament light in patients with primary chronic progressive multiple sclerosis Multiple Sclerosis, December 1, 2004; 10(6): 601 - 606. [Abstract] [PDF]
|
|
|
|
|
|
M Colucci, L Roccatagliata, E Capello, E Narciso, N Latronico, M Tabaton, and G L Mancardi The 14-3-3 protein in multiple sclerosis: a marker of disease severity Multiple Sclerosis, October 1, 2004; 10(5): 477 - 481. [Abstract] [PDF]
|
|
|
|
 |
|
 O. Lily, J. Palace, and A. Vincent Serum autoantibodies to cell surface determinants in multiple sclerosis: a flow cytometric study Brain, February 1, 2004; 127(2): 269 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Malmestrom, S. Haghighi, L. Rosengren, O. Andersen, and J. Lycke Neurofilament light protein and glial fibrillary acidic protein as biological markers in MS Neurology, December 23, 2003; 61(12): 1720 - 1725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Diem, M. Hobom, K. Maier, R. Weissert, M. K. Storch, R. Meyer, and M. Bahr Methylprednisolone Increases Neuronal Apoptosis during Autoimmune CNS Inflammation by Inhibition of an Endogenous Neuroprotective Pathway J. Neurosci., August 6, 2003; 23(18): 6993 - 7000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
January 28 Highlights Neurology, January 28, 2003; 60(2): 159 - 159. [Full Text] [PDF]
|
|
|
|
|
|
M.J. Eikelenboom, A. Petzold, R.H.C. Lazeron, E. Silber, M. Sharief, E.J. Thompson, F. Barkhof, G. Giovannoni, C.H. Polman, and B.M.J. Uitdehaag Multiple sclerosis: Neurofilament light chain antibodies are correlated to cerebral atrophy Neurology, January 28, 2003; 60(2): 219 - 223. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
