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Elevated EBNA-1 IgG in MS is associated with genetic MS risk variants
Karim L Kreft1, Gijsbert P Van Nierop1, Sandra M J Scherbeijn1
1Department of Neurology (K.L.K., G.P.V.N., M.J., R.Q.H.), MS Center ErasMS (K.L.K., M.J., R.Q.H.), Department of Viroscience (G.P.V.N., S.M.J.S., G.M.G.M.V.), and Department of Immunology (M.J., R.Q.H.), Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Neurology(R) Neuroimmunology & Neuroinflammation
|January 31, 2018
Summary
Multiple sclerosis (MS) genetic risk factors are linked to higher Epstein-Barr virus (EBV) antibody levels. Specific single nucleotide polymorphisms (SNPs) correlate with increased EBNA-1 IgG, suggesting a role in MS pathogenesis.
Area of Science:
- Immunogenetics
- Neuroimmunology
- Virology
Background:
- Epstein-Barr virus (EBV) infection is associated with an increased risk of developing multiple sclerosis (MS).
- MS is characterized by an aberrant immune response, but the role of genetic predisposition in modulating antiviral immunity remains unclear.
- Investigating the interplay between MS genetic risk polymorphisms and humoral immune responses to EBV is crucial for understanding MS etiology.
Purpose of the Study:
- To determine if MS-associated single nucleotide polymorphisms (SNPs) influence the heightened immune response to Epstein-Barr virus (EBV) observed in MS patients.
- To identify specific genetic risk factors that correlate with altered antibody levels against EBV proteins.
Main Methods:
- Quantitative measurement of serum immunoglobulin G (IgG) antibodies against EBV nuclear antigen 1 (EBNA-1) and early antigen D (EA-D) in 668 MS patients and 147 healthy controls.
- Genotyping of MS patients for known risk SNPs and analysis of associations with anti-EBV IgG levels.
- Use of anti-varicella-zoster virus (VZV) IgG as a control for non-MS-associated herpesvirus antibody levels.
Main Results:
- Patients with MS exhibited significantly higher IgG levels against EBNA-1, a latent EBV protein, compared to healthy controls.
- Increased EBNA-1 IgG levels were significantly associated with risk alleles of several MS-associated SNPs, including rs2744148 (SOX8), rs11154801 (MYB), rs1843938 (CARD11), and rs7200786 (CLEC16A/CIITA).
- No significant associations were found for EA-D or VZV IgG levels with MS risk SNPs.
Conclusions:
- Several MS-associated SNPs are significantly correlated with differential IgG levels targeting a latent EBV protein (EBNA-1).
- These findings suggest that immune-related genes associated with MS risk may orchestrate aberrant EBNA-1 IgG levels.
- The study highlights a potential genetic influence on the immune response to EBV in the context of MS.
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