OBJECTIVE: 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. METHODS: IgG levels against EBNA-1 and varicella zoster virus (VZV) as control were measured. HLA-DRB1*1501 and HLA-A*02 tagging single-nucleotide polymorphisms (SNPs) were genotyped. We assessed the associations between these SNPs and antiviral IgG titers. RESULTS: OR for abundant EBNA-1 IgG was the highest in patients with MS and intermediate in their siblings compared with spouses. We confirmed that HLA-DRB1*1501 is associated with abundant EBNA-1 IgG. After stratification for HLA-DRB1*1501, the EBNA-1 IgG gradient was still significant in patients with MS and young siblings compared with spouses. HLA-A*02 was not explanatory for EBNA-1 IgG titer gradient. No associations for VZV IgG were found. CONCLUSIONS: 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 HLA-DRB1*1501 carriership.

doi.org/10.1212/NXI.0000000000000872, hdl.handle.net/1765/129725
Neurology(R) neuroimmunology & neuroinflammation
Erasmus MC: University Medical Center Rotterdam

Mescheriakova, J.Y, van Nierop, G.P, van der Eijk, A.A. (Annemiek A.), Kreft, K.L, & Hintzen, R.Q. (2020). EBNA-1 titer gradient in families with multiple sclerosis indicates a genetic contribution. Neurology(R) neuroimmunology & neuroinflammation, 7(6). doi:10.1212/NXI.0000000000000872