EBNA-1 titer gradient in families with multiple sclerosis indicates a genetic contribution
Julia Mescheriakova, Gijsbert P. van Nierop, Annemiek A. van der Eijk, Karim L. Kreft, Rogier Q. Hintzen
Abstract
<h3>Objective</h3> In multiplex MS families, we determined the humoral immune response to Epstein-Barr virus nuclear antigen 1 (EBNA-1)-specific immunoglobulin γ (IgG) titers in patients with MS, their healthy siblings, and biologically unrelated healthy spouses and investigated the role of specific genetic loci on the antiviral IgG titers. <h3>Methods</h3> IgG levels against EBNA-1 and varicella zoster virus (VZV) as control were measured. <i>HLA-DRB1*1501</i> and <i>HLA-A*02</i> tagging single-nucleotide polymorphisms (SNPs) were genotyped. We assessed the associations between these SNPs and antiviral IgG titers. <h3>Results</h3> OR for abundant EBNA-1 IgG was the highest in patients with MS and intermediate in their siblings compared with spouses. We confirmed that <i>HLA-DRB1*1501</i> is associated with abundant EBNA-1 IgG. After stratification for <i>HLA-DRB1*1501</i>, the EBNA-1 IgG gradient was still significant in patients with MS and young siblings compared with spouses. <i>HLA-A*02</i> was not explanatory for EBNA-1 IgG titer gradient. No associations for VZV IgG were found. <h3>Conclusions</h3> In families with MS, the EBNA-1 IgG gradient being the highest in patients with MS, intermediate in their siblings, and lowest in biologically unrelated spouses indicates a genetic contribution to EBNA-1 IgG levels that is only partially explained by <i>HLA-DRB1*1501</i> carriership.