Elevated EBNA-1 IgG in MS is associated with genetic MS risk variants. Issue 6 (November 2017)

• Record Type: Journal Article
• Authors: Kreft, Karim L.; Van Nierop, Gijsbert P.; Scherbeijn, Sandra M.J.; Janssen, Malou; Verjans, Georges M.G.M.; Hintzen, Rogier Q.
• Is Part Of: Neurology. Volume 4:Issue 6(2017)
• Publication Date: 2017-11
• Subjects: Neuroimmunology -- Periodicals; Neurology -- Periodicals; 616.8
• DOI: 10.1212/NXI.0000000000000406
• Languages: English
• ISSNs: 2332-7812

Abstract

Abstract : Objective: To assess whether MS genetic risk polymorphisms (single nucleotide polymorphism [SNP]) contribute to the enhanced humoral immune response against Epstein-Barr virus (EBV) infection in patients with MS. Methods: Serum anti-EBV nuclear antigen 1 (EBNA-1) and early antigen D (EA-D) immunoglobulin γ (IgG) levels were quantitatively determined in 668 genotyped patients with MS and 147 healthy controls. Anti–varicella-zoster virus (VZV) IgG levels were used as a highly prevalent, non-MS–associated control herpesvirus. Associations between virus-specific IgG levels and MS risk SNPs were analyzed. Results: IgG levels of EBNA-1, but not EA-D and VZV, were increased in patients with MS compared with healthy controls. Increased EBNA-1 IgG levels were significantly associated with risk alleles of SNP rs2744148 (SOX8), rs11154801 (MYB), rs1843938 (CARD11), and rs7200786 (CLEC16A/CIITA) in an interaction model and a trend toward significance for rs3135388 (HLA-DRB1*1501). In addition, risk alleles of rs694739 (PRDX5/BAD) and rs11581062 (VCAM1) were independently associated and interacted with normal EBNA-1 IgG levels. None of these interactions were associated with EA-D and VZV IgG titers. Conclusions: Several MS-associated SNPs significantly correlated with differential IgG levels directed to a latent, but not a lytic EBV protein. The data suggest that the aforementioned immune-related genes orchestrate the aberrant EBNA-1 IgG levels.