The level of anti-viral antigen-specific antibodies to EBNA-1 in the serum of ms patients does not depend on the severity of the disease

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Abstract

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease leading to inevitable disability and primarily affecting the young and middle-aged population. Recent studies have shown a direct correlation between the risk of MS development and Epstein-Barr virus (EBV) infection. Analysis of the titer of EBV-specific antibodies among patients with MS and healthy donors among Russian population confirmed that MS is characterized by an increased level of serum IgG binding EBNA-1 (EBV nuclear antigen 1). The number of patients with elevated levels of EBNA-1-specific antibodies does not differ statistically significantly between two groups with diametrically opposite courses of MS: benign MS or highly active MS. It can be assumed that the primary link between EBV and the development of MS is restricted to the initiation of the disease and does not impact its severity.

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About the authors

L. А. Ovchinnikova

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS

Email: gabibov@gmail.com
Russian Federation, Moscow

S. S. Dzhelad

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS

Email: gabibov@gmail.com
Russian Federation, Moscow

Т. О. Simaniv

Research Center of Neurology

Email: gabibov@gmail.com
Russian Federation, Moscow

М. N. Zakharova

Research Center of Neurology

Email: gabibov@gmail.com
Russian Federation, Moscow

А. G. Gabibov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS; Lomonosov Moscow State University

Author for correspondence.
Email: gabibov@gmail.com

Academician

Russian Federation, Moscow; Moscow

Ya. A. Lomakin

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS

Email: yasha.l@bk.ru
Russian Federation, Moscow

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2. Rice. 1. Serum level of antigen-specific IgG to EBV fragments: binding of the chemically synthesized EBNA-1 peptide (386–405 aa)(a); binding of chemically synthesized control peptide LMP1 (aa 7–26)(b). ZD – healthy donors, MS – patients with multiple sclerosis, DRS – patients with benign multiple sclerosis, HARS – patients with highly active multiple sclerosis, ALS – patients with amyotrophic lateral sclerosis, NMOSD – patients with neuromyelitis optica spectrum disease. The red dotted line indicates the threshold optical density value, above which the serum is considered seropositive for the test antigen. The dotted green line indicates the control signal of binding of the test antigen by IVIG (pooled IgG from 1000 healthy donors) (* p < 0.05; ** p < 0.01, Pearson Chi-square).

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3. Rice. 2. The proposed scheme of participation of the Epstein-Barr virus in the development of multiple sclerosis. 1. The virus enters the human body and infects B cells. 2. There is an accumulation of viral antigens (for example, EBNA-1, VCA, etc.) and the formation of antiviral antibodies to these antigens. 3. The resulting antiviral immunoglobulins, in the process of maturation and somatic hypermutation, become cross-reactive to human neuronal antigens. EBV – Epstein-Barr virus, MS – multiple sclerosis.  

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