PT  - JOURNAL ARTICLE
AU  - Mescheriakova, Julia Y.
AU  - van Nierop, Gijsbert P.
AU  - van der Eijk, Annemiek A.
AU  - Kreft, Karim L.
AU  - Hintzen, Rogier Q.
TI  - EBNA-1 titer gradient in families with multiple sclerosis indicates a genetic contribution
AID  - 10.1212/NXI.0000000000000872
DP  - 2020 Nov 05
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e872
VI  - 7
IP  - 6
4099  - http://nn.neurology.org/content/7/6/e872.short
4100  - http://nn.neurology.org/content/7/6/e872.full
SO  - Neurol Neuroimmunol Neuroinflamm2020 Nov 05; 7
AB  - 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.EBNA-1=EBV nuclear antigen 1; EBV=Epstein-Barr virus; IgG=immunoglobulin; SNP=single-nucleotide polymorphism; VCA=virus capsid antigen; VZV=varicella zoster virus