NEUROLOGY 2004;62:2277-2282
© 2004 American Academy of Neurology
An altered immune response to Epstein-Barr virus in multiple sclerosis
A prospective study
P. Sundström, MD PhD,
P. Juto, MD PhD,
G. Wadell, MD PhD,
G. Hallmans, MD PhD,
A. Svenningsson, MD PhD,
L. Nyström, PhD,
J. Dillner, MD PhD and
L. Forsgren, MD PhD
From the Department of Neurology (Drs. Sundström, Svenningsson, and Forsgren), the Department of Virology (Drs. Juto and Wadell), Umeå University Hospital; the Department of Public Health and Clinical Medicine, Nutritional Research (Dr. Hallmans) and Epidemiology (Dr. Nyström), Umeå University; and the Department of Medical Microbiology (Dr. Dillner), Malmö University Hospital, Lunds University, Sweden.
Address correspondence and reprint requests to Dr. Peter Sundström, Department of Neurology, Norrlands University, Umeå 590185, Sweden; e-mail: peter.sundstrom{at}neuro.umu.se
Objective: To investigate the association between human herpesviruses and multiple sclerosis (MS), as well as between measles virus and MS.
Methods: The authors identified prospectively collected serum samples from 73 MS cases and retrospective sera from 161 MS cases in two population-based serum bank registers. Analyses of IgG antibody responses in cases and matched referents were performed for Epstein-Barr virus (EBV [EBNA-1 and VCA]), human herpesvirus 6 (HHV-6), herpes simplex virus (HSV), varicella zoster virus (VZV), and measles.
Results: All cases showed signs of past EBV infection. High activity to EBNA-1 and HHV-6 significantly (borderline significance for HHV-6) increased the risk for MS in prospective sera. A discrepancy between activities to EBNA-1 and VCA was striking in MS samples collected less than 5 years before relapsing-remitting MS onset, where high activity to EBNA-1 significantly increased, and high VCA activity significantly decreased the risk for MS. There was no support for major causal roles for HSV, VZV, or measles.
Conclusion: Individuals who will develop MS exhibit an altered immune response against the EBV virus characterized by a high IgG activity to EBNA-1 in the absence of high activity to VCA, this being most pronounced in the 5-year period preceding MS onset.
Received October 1, 2003.
Accepted in final form February 11, 2004.
This article has been cited by other articles:
|
|
|
|
 
M. P. Pender
Does Epstein-Barr virus infection in the brain drive the development of multiple sclerosis?
Brain,
December 1, 2009;
132(12):
3196 - 3198.
[Full Text]
[PDF]
|
|
|
|
|
|
|
2009 ACTRIMS ABSTRACTS: Oral Presentations
Multiple Sclerosis,
November 1, 2009;
15(11):
1387 - 1395.
[PDF]
|
|
|
|
|
|
|
R. A. Farrell, D. Antony, G. R. Wall, D. A. Clark, L. Fisniku, J. Swanton, Z. Khaleeli, K. Schmierer, D. H. Miller, and G. Giovannoni
Humoral immune response to EBV in multiple sclerosis is associated with disease activity on MRI
Neurology,
July 7, 2009;
73(1):
32 - 38.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Lunemann and A. Ascherio
Immune responses to EBNA1: Biomarkers in MS?
Neurology,
July 7, 2009;
73(1):
13 - 14.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R Zivadinov, M Zorzon, B Weinstock-Guttman, M Serafin, A Bosco, A Bratina, C Maggiore, A Grop, M A Tommasi, B Srinivasaraghavan, et al.
Epstein-Barr virus is associated with grey matter atrophy in multiple sclerosis
J. Neurol. Neurosurg. Psychiatry,
June 1, 2009;
80(6):
620 - 625.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Mikaeloff, G. Caridade, S. Suissa, M. Tardieu, and on Behalf of the KIDSEP Study Group
Clinically Observed Chickenpox and the Risk of Childhood-onset Multiple Sclerosis
Am. J. Epidemiol.,
May 15, 2009;
169(10):
1260 - 1266.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M P Pender, P A Csurhes, A Lenarczyk, C M M Pfluger, and S R Burrows
Decreased T cell reactivity to Epstein-Barr virus infected lymphoblastoid cell lines in multiple sclerosis
J. Neurol. Neurosurg. Psychiatry,
May 1, 2009;
80(5):
498 - 505.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lindsey, L. Hatfield, M. Crawford, and S Patel
Quantitative PCR for Epstein-Barr virus DNA and RNA in multiple sclerosis
Multiple Sclerosis,
February 1, 2009;
15(2):
153 - 158.
[Abstract]
[PDF]
|
|
|
|
|
|
|
P Sundstrom, L Nystrom, E Jidell, and G Hallmans
EBNA-1 reactivity and HLA DRB1*1501 as statistically independent risk factors for multiple sclerosis: a case-control study
Multiple Sclerosis,
September 1, 2008;
14(8):
1120 - 1122.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. D. Lunemann, I. Jelcic, S. Roberts, A. Lutterotti, B. Tackenberg, R. Martin, and C. Munz
EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-{gamma} and IL-2
J. Exp. Med.,
August 4, 2008;
205(8):
1763 - 1773.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Jilek, M. Schluep, P. Meylan, F. Vingerhoets, L. Guignard, A. Monney, J. Kleeberg, G. Le Goff, G. Pantaleo, and R. A. Du Pasquier
Strong EBV-specific CD8+ T-cell response in patients with early multiple sclerosis
Brain,
July 1, 2008;
131(7):
1712 - 1721.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. De Jager, K. C. Simon, K. L. Munger, J. D. Rioux, D. A. Hafler, and A. Ascherio
Integrating risk factors: HLA-DRB1*1501 and Epstein-Barr virus in multiple sclerosis
Neurology,
March 25, 2008;
70(13_Part_2):
1113 - 1118.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Habek, V. V Brinar, and S. Hajnsek
The association of multiple sclerosis and Hodgkin's disease: the role of Epstein--Barr virus infection
Multiple Sclerosis,
March 1, 2008;
14(2):
284 - 287.
[Abstract]
[PDF]
|
|
|
|
|
|
|
B. Serafini, B. Rosicarelli, D. Franciotta, R. Magliozzi, R. Reynolds, P. Cinque, L. Andreoni, P. Trivedi, M. Salvetti, A. Faggioni, et al.
Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain
J. Exp. Med.,
November 26, 2007;
204(12):
2899 - 2912.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Lunemann, T. Kamradt, R. Martin, and C. Munz
Epstein-Barr Virus: Environmental Trigger of Multiple Sclerosis?
J. Virol.,
July 1, 2007;
81(13):
6777 - 6784.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T.R. Nielsen, M. Pedersen, K. Rostgaard, M. Frisch, and H. Hjalgrim
Correlations between Epstein-Barr virus antibody levels and risk factors for multiple sclerosis in healthy individuals
Multiple Sclerosis,
April 1, 2007;
13(3):
420 - 423.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. R. Nielsen, K. Rostgaard, N. M. Nielsen, N. Koch-Henriksen, S. Haahr, P. S. Sorensen, and H. Hjalgrim
Multiple Sclerosis After Infectious Mononucleosis
Arch Neurol,
January 1, 2007;
64(1):
72 - 75.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Pohl, B. Krone, K. Rostasy, E. Kahler, E. Brunner, M. Lehnert, H. -J. Wagner, J. Gartner, and F. Hanefeld
High seroprevalence of Epstein-Barr virus in children with multiple sclerosis
Neurology,
December 12, 2006;
67(11):
2063 - 2065.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Lunemann, N. Edwards, P. A. Muraro, S. Hayashi, J. I. Cohen, C. Munz, and R. Martin
Increased frequency and broadened specificity of latent EBV nuclear antigen-1-specific T cells in multiple sclerosis
Brain,
June 1, 2006;
129(6):
1493 - 1506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. N. DeLorenze, K. L. Munger, E. T. Lennette, N. Orentreich, J. H. Vogelman, and A. Ascherio
Epstein-Barr Virus and Multiple Sclerosis: Evidence of Association From a Prospective Study With Long-term Follow-up
Arch Neurol,
June 1, 2006;
63(6):
839 - 844.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. I. Levin, K. L. Munger, M. V. Rubertone, C. A. Peck, E. T. Lennette, D. Spiegelman, and A. Ascherio
Temporal Relationship Between Elevation of Epstein-Barr Virus Antibody Titers and Initial Onset of Neurological Symptoms in Multiple Sclerosis
JAMA,
May 25, 2005;
293(20):
2496 - 2500.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ruprecht and H. Perron
Exposure to Infant Siblings During Early Life and Risk of Multiple Sclerosis
JAMA,
May 4, 2005;
293(17):
2089 - 2089.
[Full Text]
[PDF]
|
|
|
|
