Multiple Sclerosis

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lopatinskaya, L
Right arrow Articles by Nagelkerken, L
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lopatinskaya, L
Right arrow Articles by Nagelkerken, L
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Multiple Sclerosis, Vol. 12, No. 6, 704-709 (2006)
DOI: 10.1177/1352458506070826
© 2006 SAGE Publications

Mediators of apoptosis Fas and FasL predict disability progression in multiple sclerosis over a period of 10 years

L Lopatinskaya

Division of Biomedical Research, TNO Quality of Life, P.O. Box 2215, 2301 CE, Leiden, The Netherlands, Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands

J Zwemmer

Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands

B Uitdehaag

Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands

K Lucas

Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands

C Polman

Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands

L Nagelkerken

Division of Biomedical Research, TNO Quality of Life, P.O. Box 2215, 2301 CE, Leiden, The Netherlands, am.nagelkerken{at}pg.tno.nl

TNF-{alpha}, IL-12p35, IL-12p40, IL-4, IL-10, TGF-ß1, CCR3, CXCR3, CCR5, Fas and FasL mRNA levels in PBMC of 25 multiple sclerosis (MS) patients were quantified at baseline by real-time PCR according to a post-hoc study design. The baseline values of the different markers were analysed with respect to their correlation with the increase in disability over a period of 10 years. High levels of Fas mRNA were associated with a favourable disease course in relapsing-remitting (RR) MS (R2 = 0.74, P = 0.0001, n = 13), as measured by the Expanded Disability Status Scale (EDSS); high levels of FasL mRNA were associated with relatively mild disease progression (R2 = 0.86, P = 0.0001, n = 12) in secondary progressive (SP) MS. These findings suggest that Fas-mediated apoptosis plays a major role in the mechanism underlying long-term disease progression in MS.

Key Words: apoptosis • chemokines • cytokines • EDSS • Fas • MS

References

  • Barkhof F. The clinico-radiological paradox in multiple sclerosis revisited . Curr Opin Neurol 2002; 15: 239-245 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Kappos L, Stadt D, Keil W, Ratzka M, Heitzer T, Schneiderbanger-Grygier S. An attempt to quantify magnetic resonance imaging in multiple sclerosis-correlation with clinical parameters . Neurosurg Rev 1987; 10: 133-135 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Kappos L, Moeri D, Radue EW, Schoetzau A, Schweikert K, Barkhof F, et al. Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability impairment in multiple sclerosis: a meta-analysis . Lancet 1999; 353; 964-969 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Rovaris M, Agosta F, Sormani MP, Inglese M, Martinelli V, Comi G, et al. Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study . Brain 2003; 126: 2323-2332 .[Abstract/Free Full Text]
  • Brex PA, Ciccarelli O, O’Riordan JI, Sailer M, Thompson AJ, Miller DH. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis . N Engl J Med 2002; 346: 158-164 .[Abstract/Free Full Text]
  • Fisher E, Rudick RA, Cutter G, Baier M, Miller D, Weinstock-Guttman B, et al. Relationship between brain atrophy and disability: an 8-years follow-up study of multiple sclerosis patients . Mult Scler 2000; 6: 373-377 .[Abstract/Free Full Text]
  • Santos AC, Narayanan S, de Stefano N, Tartaglia MC, Francis SJ, Arnaoutelis R, et al. Magnetization transfer can predict clinical evolution in patients with multiple sclerosis . J Neurol 2002; 249: 662-668 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Kalkers NF, Bergers E, Castelijns JA, van Walderveen MA, Bot JC, Ader HJ, et al. Optimizing the association between disability and biological markers in MS . Neurology 2001; 57: 1253-1258 .[Abstract/Free Full Text]
  • van Veen T, Kalkers NF, Crusius JB, van Winsen L, Barkhof F, Jongen PJ, et al. The FAS-670 polymorphism influences susceptibility to multiple sclerosis . J Neuroimmunol 2002; 128: 95-100 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Caillier S, Barcellos LF, Baranzini SE, Swerdlin A, Lincoln RR, Steinman L, et al. Osteopontin polymorphisms and disease course in multiple sclerosis . Genes Immunol 2003; 4: 312-315 .
  • van Boxel-Dezaire AH, Hoff SC, van Oosten BW, Verweij CL, Dräger AM, Ader HJ, et al. Decreased IL-10 and increased IL-12p40 mRNA are associated with disease activity and characterize different disease stages in multiple sclerosis . Ann Neurol 1999; 45: 695-703 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Vogt MH, Lopatinskaya L, Smits M, Polman CH, Nagelkerken L. Elevated osteopontin levels in active relapsing-remitting multiple sclerosis . Ann Neurol 2003; 53: 819-822 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Lopatinskaya L, van Boxel-Dezaire AH, Barkhof F, Polman CH, Lucas CJ, Nagelkerken L. The development of clinical activity in relapsing-remitting MS is associated with a decrease of FasL mRNA and an increase of Fas mRNA in peripheral blood . J Neuroimmunol 2003; 138: 123-131 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Comi C, Leone M, Bonissoni S, DeFranco S, Bottarel F, Mezzatesta C, et al. Defective T cell Fas function in patients with multiple sclerosis . Neurology 2000; 55: 921-927 .[Abstract/Free Full Text]
  • Huang W-X, Huang MP, Gomes MA, Hillert J. Apoptosis mediators FasL and TRAIL are upregulated in peripheral blood mononuclear cells in MS . Neurology 2000; 55: 928-934 .[Abstract/Free Full Text]
  • Ichikawa H, Ota K, Iwata M. Increased Fas antigen on T cells in multiple sclerosis . J Neuroimmunol 1996; 71: 125-129 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Zipp F, Otzelberger K, Dichgans J, Martin R, Weller M. Serum CD95 of relapsing-remitting multiple sclerosis patients protects from CD95-mediated apoptosis . J Neuroimmunol 1998; 86: 151-154 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Kahl KG, Kruse N, Toyka KV, Rieckmann P. Serial analysis of cytokine mRNA profiles in whole blood samples from patients with early multiple sclerosis . J Neurol Sci 2002; 200: 53-55 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Makhlouf K, Weiner HL, Khoury SJ. Increased percentage of IL-12+monocytes in the blood correlates with the presence of active MRI lesions in MS . J Neuroimmunol 2001; 119: 145-149 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Balashov KE, Rottman JB, Weiner HL, Hancock WW. CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and their ligands MIP-1a and IP-10 are expressed in demyelinating brain lesions . Proc Natl Acad Sci USA 1999; 96: 6873-6878 .[Abstract/Free Full Text]
  • Eikelenboom MJ, Killestein J, Izeboud T, Kalkers NF, van Lier RA, Barkhof F, et al. Chemokine receptor expression on T cells is related to new lesion development in multiple sclerosis . J Neuroimmunol 2002; 133: 225-232 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Baranzini SE, Elfstrom C, Chang SY, Butunoi C, Murray R, Higuchi R, et al. Transcriptional analysis of multiple sclerosis brain lesions reveals a complex pattern of cytokine expression . J Immunol 2000; 165: 6576-6582 .[Abstract/Free Full Text]
  • van Oosten BW, Lai M, Hodgkinson S, Barkhof F, Miller DH, Moseley IF, et al. Treatment of multiple sclerosis with the monoclonal anti-CD4 antibody cMT412: results of a randomized, double-blind, placebo-controlled, MR-monitored phase II trial . Neurology 1997; 49: 351-357 .[Abstract/Free Full Text]
  • Lechner-Scott J, Kappos L, Hofman M, Polman CH, Ronner H, Montalban X, et al. Can the Expanded Disability Status Scale be assessed by telephone? Mult Scler 2003; 9: 154-159 .[Abstract/Free Full Text]
  • Pender MP. Genetically determined failure of activation-induced apoptosis of autoreactive T cells as a cause of multiple sclerosis . Lancet 1998; 351: 978-981 .[ISI][Medline] [Order article via Infotrieve]
  • Sharief MK. Impaired Fas-independent apoptosis of T lymphocytes in patients with multiple sclerosis . J Neuroimmunol 2000; 113: 236-243 .[CrossRef]
  • Zang YC, Kozovska MM, Hong J, Li S, Mann S, Killian JM, et al. Impaired apoptotic deletion of myelin basic protein-reactive T cells in patients with multiple sclerosis . Eur J Immunol 1999; 29: 1692-1700 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Achiron A, Gurevich M, Friedman N, Kaminski N, Mandel M. Blood transcriptional signatures of MS: unique gene expression of disease activity . Ann Neurol 2004; 55: 410-417 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Bechmann I, Steiner B, Gimsa U, Mor G, Wolf S, Beyer M, et al. Astrocyte-induced T cell elimination is CD95 ligand dependent . J Neuroimmunol 2002; 132: 60-65 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Magnus T, Chan A, Savill J, Toyka KV, Gold R. Phagocytic removal of apoptotic, inflammatory lymphocytes in the central nervous system by microglia and its functional implications . J Neuroimmunol 2002; 130: 1-9 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Kanwar JR, Kanwar RK, Krissansen GW. Simultaneous neuroprotection and blockade of inflammation reverses autoimmune encephalomyelitis . Brain 2004; 127: 1313-1331 .[Abstract/Free Full Text]
  • Todaro M, Zeuner A, Stassi G. Role of apoptosis in autoimmunity . J Clin Immunol 2004; 24: 1-11 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Banisor I, Kalman B. Bcl-2 and its homologues in the brain of patients with multiple sclerosis . Mult Scler 2004; 10: 176-181 .[Abstract/Free Full Text]
  • Wandinger KP, Lunemann JD, Wengert O, Bellmann-Strobl J, Aktas O, Weber A, et al. TNF-related apoptosis inducing ligand (TRAIL) as a potential response marker for interferon-beta treatment in multiple sclerosis . Lancet 2003; 361: 2036-2043 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Farrell R, Heaney D, Giovannoni G. Emerging therapies in multiple sclerosis . Expert Opin Emerg Drugs 2005; 10: 797-816 .[CrossRef][Medline] [Order article via Infotrieve]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lopatinskaya, L
Right arrow Articles by Nagelkerken, L
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lopatinskaya, L
Right arrow Articles by Nagelkerken, L
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?