Epstein-Barr virus-specific antibody response in cerebrospinal fluid and serum of patients with multiple sclerosis

Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein—Barr virus (EBV) IgG were measured by enzyme-linked immunosorbent assay in 80 relapsing—remitting multiple sclerosis patients grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Eighty patients with other inflammatory neurological disorders (OIND) and 80 patients with non-inflammatory neurological disorders (NIND) served as neurological controls. Cerebrospinal fluid concentrations were higher in OIND than in multiple sclerosis ( p < 0.0001) and NIND ( p < 0.01) for anti-viral-capsid-antigen (anti-VCA) IgG, in multiple sclerosis than in NIND ( p < 0.01) and in OIND than in NIND ( p < 0.05) for anti-EBV nuclear antigen-1 (EBNA-1) IgG. Serum levels were more elevated in OIND than in multiple sclerosis ( p < 0.05) and in MRI inactive than in MRI active multiple sclerosis ( p < 0.0001) for anti-VCA IgG, and in multiple sclerosis than in OIND and NIND ( p < 0.01) for anti-EBNA-1 IgG. Serum titres of anti-VCA and anti-EBNA-1 IgG were also positively ( p < 0.05) and inversely ( p < 0.001) correlated, respectively, with the Expanded Disability Status Scale. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a limited number of multiple sclerosis patients and controls (range from 1.3 to 6.3%). These findings do not support a direct pathogenetic role of EBV-targeted humoral immune response in multiple sclerosis.

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Epstein-Barr Virus Specific Antibody Response in Multiple Sclerosis Patients during 21 Months of Natalizumab Treatment

Disease Markers ◽

10.1155/2015/901312 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Massimiliano Castellazzi ◽

Serena Delbue ◽

Francesca Elia ◽

Matteo Gastaldi ◽

Diego Franciotta ◽

...

Keyword(s):

Multiple Sclerosis ◽

Specific Antibody ◽

Epstein Barr Virus ◽

Serum Levels ◽

Nuclear Antigen ◽

Barr Virus ◽

Natalizumab Treatment ◽

Virus Specific Antibody ◽

Epstein Barr ◽

Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. Natalizumab, a humanized anti-α4 integrin monoclonal antibody, is a highly effective treatment approved for MS. An association between MS and an exposure to Epstein-Barr Virus (EBV) sustained by the levels of antiviral capsid antigen (VCA) and anti-Epstein-Barr nuclear antigen-1 (EBNA-1) IgG has been described. Our goal was to verify the utility of EBV-specific IgG as a marker in Natalizumab treated MS. Twenty patients (17 female and 3 male) in treatment with Natalizumab were enrolled. Serum levels of anti-VCA and anti-EBNA-1 IgG were determined and expressed as arbitrary units (AU) before treatment and every three months for 21 months of therapy. Anti-VCA IgG levels were increased at the 15th month (235410 ± 196712 AU) comparing with the 3rd (98146 ± 47145 AU) and the 6th (109866 ± 52270 AU) months of therapyp<0.05. No significant differences were found for serum anti-EBNA-1 IgG levels. Our data indicate that a transient, self-limited, EBV reactivation can occur in MS during Natalizumab therapy but our results do not support the use of serum EBV-specific antibody levels as biomarkers for monitoring therapeutic response to Natalizumab in the course of MS.

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Cerebrospinal fluid T cells from multiple sclerosis patients recognize autologous Epstein-Barr virus–transformed B cells

Journal of NeuroVirology ◽

10.1080/13550280490261671 ◽

2004 ◽

Vol 10 (1) ◽

pp. 52-56 ◽

Cited By ~ 28

Author(s):

Trygve Holmøy ◽

Frode Vartdal

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Cerebrospinal Fluid ◽

B Cells ◽

Epstein Barr Virus ◽

Barr Virus ◽

Epstein Barr ◽

Multiple Sclerosis Patients

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Sa.16. Multiple Sclerosis Patients Exhibit a Unique Humoral Response to the Epstein-Barr Virus Nuclear Antigen-1

Clinical Immunology ◽

10.1016/j.clim.2006.04.248 ◽

2006 ◽

Vol 119 ◽

pp. S110

Author(s):

Latisha Heinlen ◽

Micah McClain ◽

Andrew Pachner ◽

John Harley ◽

Judith James

Keyword(s):

Multiple Sclerosis ◽

Epstein Barr Virus ◽

Humoral Response ◽

Nuclear Antigen ◽

Barr Virus ◽

Epstein Barr ◽

Multiple Sclerosis Patients

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Antiviral immune response in patients with multiple sclerosis and healthy siblings

Multiple Sclerosis Journal ◽

10.1177/1352458509357066 ◽

2010 ◽

Vol 16 (3) ◽

pp. 355-358 ◽

Cited By ~ 15

Author(s):

M. Comabella ◽

X. Montalban ◽

A. Horga ◽

B. Messmer ◽

K. Kakalacheva ◽

...

Keyword(s):

Multiple Sclerosis ◽

Measles Virus ◽

Epstein Barr Virus ◽

Virus Antigen ◽

Nuclear Antigen ◽

Antiviral Immune Response ◽

Barr Virus ◽

Healthy Siblings ◽

Epstein Barr ◽

Multiple Sclerosis Patients

The objective of this study was to determine the immune responses to candidate viral triggers of multiple sclerosis in patients and healthy siblings raised in the same family household. Virus antigen-specific IgG responses to Epstein—Barr virus-derived gene products as well as to human herpersvirus-6, human cytomegalovirus, and measles virus were evaluated in 25 multiple sclerosis patients and compared with 49 healthy full-siblings. IgG responses to the latent Epstein—Barr virus-encoded nuclear antigen-1 (EBNA1) were selectively increased in individuals with multiple sclerosis compared with their unaffected siblings. We conclude that elevated IgG responses towards EBNA1 are associated with the development of multiple sclerosis.

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Investigation on the serum antibodies levels against Epstein-Barr virus in pulmonary lymphoepithelioma-like carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18186 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18186-18186

Author(s):

S. Niraula ◽

Y. S. Zong ◽

L. Z. Zhai ◽

C. C. Guo ◽

T. Y. Lin

Keyword(s):

Epstein Barr Virus ◽

High Titer ◽

Serum Levels ◽

Small Sample ◽

Nuclear Antigen ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Antibodies ◽

Barr Virus ◽

Antigen Complex ◽

Epstein Barr

18186 Background: Pulmonary lymphoepithelioma-like carcinoma (PLELC) belongs to large cell sub-type of non-small cell lung cancer (NSCLC) with just about 160 cases reported previously. Its epidemiology, prognosis and therapeutic approach is evidently different from other NSCLCs. EBV infection is seen in 100% of Asian PLELC patients whenever tested. The aim of this study was to analyze serum antibodies level against EBV in PLELC patients. Methods: Sera of all seven patients with re-confirmed PLELC from a single institute in Canton, China in the past 4 years were collected. Serum levels of 8 different antibodies against EBV (Epstein-Barr virus): EBNA1 (EBV nuclear antigen 1- IgA and IgG), Zta (Bam Z transactivator antigen-IgA and IgG), VCA-p18 (Viral capsid antigen-p18-IgA and IgG), VCA-antigen complex (VCA-IgA) and Early antigen complex (EA-IgA ) were measured in each of these patients using enzyme-linked immunosorbent assay and Immunoenzymatic assay respectively. Results: Out of 7 cases, 6 showed high EBNA-1 level, 4 showed high zta, 3 showed high VCA-p18, 3 showed high titer of VCA complex and 2 showed high EA complex titer ( Table 1 ) Conclusions: Though small sample size, this is the first study in this depth ever to conclude that sera of all Asian patients with pulmonary LELC have high antibody titers against EBV. The infection mainly is latency II type as seen in Nasopharyngeal carcinoma and Hodgkin’s disease as well. A small portion of PLELC express lytic products such as Zta, EA and VCA. The authors assume that pre-therapeutic measurement of serum levels of anti-EBV antibodies (at least 2 kinds) is highly warranted in suspected Asian NSCLC patients. Positive result strongly puts PLELC into differential diagnosis. [Table: see text] No significant financial relationships to disclose.

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Epstein–Barr virus nuclear antigen-1 B-cell epitopes in multiple sclerosis twins

Multiple Sclerosis Journal ◽

10.1177/1352458511410515 ◽

2011 ◽

Vol 17 (11) ◽

pp. 1290-1294 ◽

Cited By ~ 19

Author(s):

R Mechelli ◽

J Anderson ◽

D Vittori ◽

G Coarelli ◽

V Annibali ◽

...

Keyword(s):

Multiple Sclerosis ◽

B Cell ◽

Epstein Barr Virus ◽

Nuclear Antigen ◽

Enzyme Linked Immunosorbent Assay ◽

B Cell Epitopes ◽

Barr Virus ◽

Rich Domain ◽

Epstein Barr ◽

Mz Twins

Background: Compared with quantitative observations, the search for qualitative changes that may characterize the immune response to Epstein–Barr virus (EBV) in multiple sclerosis (MS) has been less intense. Objective: To examine the B-cell epitopes of antibodies against the Epstein–Barr nuclear antigen-1 (EBNA-1) and their relevance for MS, through a study in disease-discordant identical twins. Methods: We evaluated the antibodies to all unique, maximally overlapping octapeptides of EBNA-1 in 12 pairs of monozygotic (MZ) twins (9 MS-discordant, 3 healthy), 3 non-twin patients and 2 healthy subjects. All except one of the patients were untreated. The EBV serology of these individuals had been assessed in advance using commercially available and in-house enzyme-linked immunosorbent assay (ELISA) kits, including assays for antibodies against select peptides of EBNA-1: EBNA-72 (GAGGGAGAGG) and EBNA-206 (EADYFEYHQEGGPDGE). Results: The glycine–alanine rich domain of EBNA-1 was immunodominant in all subjects. Compared with healthy individuals, and similarly to what has been described in infectious mononucleosis (IM) patients, affected co-twins and non-twin patients had a significantly increased response to another EBNA-1 epitope (aa. 401–411). Conclusion: In a study that controls for confounders, our data focus an EBNA-1 specificity that may be associated with MS pathogenesis.

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