Contributions
Abstract: EP1430
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - MS and infections
The complex etiology of multiple sclerosis (MS) consists of both genetic and environmental factors like Epstein-Barr virus (EBV) infection. About 100 mainly immune related single nucleotide polymorphisms (SNP) increase the risk of developing MS. We hypothesized that these SNP contribute to enhanced humoral immune response against EBV in MS patients.
Serum IgG levels against EBV latency-associated nuclear antigen-1 (EBNA-1) and lytic early antigen-D (EA-D) were determined in 668 MS patients and 147 healthy controls who were genotyped for 78 of 100 MS-associated SNPs using Sequenom and Illumina platform. Anti-varicella zoster virus (VZV) IgG levels were analyzed in parallel. Associations between virus-specific IgG levels and MS risk SNP (n=78) were analyzed.
IgG levels to EBNA-1, but not EA-D and VZV, are increased in MS patients compared to HC. Increased EBNA-1 IgG levels were significantly associated with risk alleles of both rs3135388 (HLA-DRB1*1501) and the interacted SNP rs2744148 (SOX8), rs11154801 (MYB), rs1843938 (CARD11) and rs7200786 (CLEC16A). Additionally, risk alleles of rs694739 (PRDX5) and rs11581062 (VCAM1) were independently associated with low EBNA-1 IgG levels. None of these SNP were associated with EA-D and VZV IgG titers. Notably, VCAM1-PRDX5 interactions counteracted HLA-DRB1*1501 association on increased EBNA-1 IgG titers.
In conclusion, several MS-associated SNPs were significantly associated 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 in MS patients.
Disclosure: Karim L. Kreft: nothing to disclose
Gijsbert P. Van Nierop: Funded by the Dutch MS Research Foundation
Sandra M.J. Scherbeijn: nothing to disclose
Georges M.G.M. Verjans: funded by Public Health Services grant AG032958 from the National Institutes of Health and Niedersachsen-Research Network on Neuroinfectiology of the Ministry of Science and Culture of Lower Saxony, Germany
Rogier Q. Hintzen: Funded by the Dutch MS Research Foundation
Abstract: EP1430
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - MS and infections
The complex etiology of multiple sclerosis (MS) consists of both genetic and environmental factors like Epstein-Barr virus (EBV) infection. About 100 mainly immune related single nucleotide polymorphisms (SNP) increase the risk of developing MS. We hypothesized that these SNP contribute to enhanced humoral immune response against EBV in MS patients.
Serum IgG levels against EBV latency-associated nuclear antigen-1 (EBNA-1) and lytic early antigen-D (EA-D) were determined in 668 MS patients and 147 healthy controls who were genotyped for 78 of 100 MS-associated SNPs using Sequenom and Illumina platform. Anti-varicella zoster virus (VZV) IgG levels were analyzed in parallel. Associations between virus-specific IgG levels and MS risk SNP (n=78) were analyzed.
IgG levels to EBNA-1, but not EA-D and VZV, are increased in MS patients compared to HC. Increased EBNA-1 IgG levels were significantly associated with risk alleles of both rs3135388 (HLA-DRB1*1501) and the interacted SNP rs2744148 (SOX8), rs11154801 (MYB), rs1843938 (CARD11) and rs7200786 (CLEC16A). Additionally, risk alleles of rs694739 (PRDX5) and rs11581062 (VCAM1) were independently associated with low EBNA-1 IgG levels. None of these SNP were associated with EA-D and VZV IgG titers. Notably, VCAM1-PRDX5 interactions counteracted HLA-DRB1*1501 association on increased EBNA-1 IgG titers.
In conclusion, several MS-associated SNPs were significantly associated 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 in MS patients.
Disclosure: Karim L. Kreft: nothing to disclose
Gijsbert P. Van Nierop: Funded by the Dutch MS Research Foundation
Sandra M.J. Scherbeijn: nothing to disclose
Georges M.G.M. Verjans: funded by Public Health Services grant AG032958 from the National Institutes of Health and Niedersachsen-Research Network on Neuroinfectiology of the Ministry of Science and Culture of Lower Saxony, Germany
Rogier Q. Hintzen: Funded by the Dutch MS Research Foundation