Contributions
Abstract: P1008
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 17 Environmental factors
Background and objective: Multiple sclerosis (MS) sometimes clusters in families where several individuals are affected and some are at higher risk of developing MS. Little is known about the shared microenvironment in these families, including infection with Epstein-Barr virus (EBV). In particular, EBV nuclear antigen-1 (EBNA-1) specific IgG levels were shown to be associated with increased risk of MS. Recently, genetic loci influencing both EBNA-1 IgG titers and MS risk were identified. The aim of our study was to determine the immune response to EBV in patients, their healthy siblings and unrelated spouses, and investigate the role of the HLA-DR and non-HLA genetic loci on the EBNA-1 IgG titers.
Methods: IgG levels against EBNA-1 and Varicella Zoster Virus (VZV) as control were measured in sera of participants. In samples negative for EBNA-1, anti-VCA IgG were measured to ascertain EBV serostatus. Loci at 1p22.1(rs11808092), 3p24.1 (rs427221), 3q13.33(rs2255214), and 10p15.1(rs12722561) and 1 loci in HLA-class II region (rs9271366) were genotyped in all subjects. Generalized linear models were used to assess associations between genetic loci and EBNA-1 IgG titers.
Results: MS patients (305) were younger and more often females compared to their non-affected siblings (198) and unrelated healthy spouses (174). EBV seroprevalence was higher in MS patients than in siblings and controls. No differences in VZV seroprevalence were observed. There was a gradient in EBNA-1 IgG titer: MS patients > siblings > spouse controls (p< 0.0001, adjusted for age and sex). MS patients, siblings and spouses with the HLA-DR risk allele (G) had higher EBNA-1 IgG titers than non-risk allele carriers. HLA-DR G-allele frequency was 0.39 in MS patients, 0.28 in siblings and 0.17 in spouses (p< 0.0001). No other non-HLA loci were associated with EBNA-1 IgG titers in MS patients, siblings or spouses, even not after stratification on the HLA-DR status.
Conclusions: Despite shared microenvironment, MS patients differ from their siblings in their increased IgG response to EBNA-1.Compared to unrelated controls also siblings show an elevated EBNA-1 IgG. Likely, the presence of HLA-DR is responsible for these findings.
Disclosure:
JY Mescheriakova reports no disclosures.
GP van Nierop reports no disclosures.
J Klaasse reports no disclosures.
SMJ Scherbeijn reports no disclosures.
GMGM Verjans reports no disclosures.
AA Baltissen-van der Eijk reports no disclosures.
RQ Hintzen reports no disclosures.
Abstract: P1008
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 17 Environmental factors
Background and objective: Multiple sclerosis (MS) sometimes clusters in families where several individuals are affected and some are at higher risk of developing MS. Little is known about the shared microenvironment in these families, including infection with Epstein-Barr virus (EBV). In particular, EBV nuclear antigen-1 (EBNA-1) specific IgG levels were shown to be associated with increased risk of MS. Recently, genetic loci influencing both EBNA-1 IgG titers and MS risk were identified. The aim of our study was to determine the immune response to EBV in patients, their healthy siblings and unrelated spouses, and investigate the role of the HLA-DR and non-HLA genetic loci on the EBNA-1 IgG titers.
Methods: IgG levels against EBNA-1 and Varicella Zoster Virus (VZV) as control were measured in sera of participants. In samples negative for EBNA-1, anti-VCA IgG were measured to ascertain EBV serostatus. Loci at 1p22.1(rs11808092), 3p24.1 (rs427221), 3q13.33(rs2255214), and 10p15.1(rs12722561) and 1 loci in HLA-class II region (rs9271366) were genotyped in all subjects. Generalized linear models were used to assess associations between genetic loci and EBNA-1 IgG titers.
Results: MS patients (305) were younger and more often females compared to their non-affected siblings (198) and unrelated healthy spouses (174). EBV seroprevalence was higher in MS patients than in siblings and controls. No differences in VZV seroprevalence were observed. There was a gradient in EBNA-1 IgG titer: MS patients > siblings > spouse controls (p< 0.0001, adjusted for age and sex). MS patients, siblings and spouses with the HLA-DR risk allele (G) had higher EBNA-1 IgG titers than non-risk allele carriers. HLA-DR G-allele frequency was 0.39 in MS patients, 0.28 in siblings and 0.17 in spouses (p< 0.0001). No other non-HLA loci were associated with EBNA-1 IgG titers in MS patients, siblings or spouses, even not after stratification on the HLA-DR status.
Conclusions: Despite shared microenvironment, MS patients differ from their siblings in their increased IgG response to EBNA-1.Compared to unrelated controls also siblings show an elevated EBNA-1 IgG. Likely, the presence of HLA-DR is responsible for these findings.
Disclosure:
JY Mescheriakova reports no disclosures.
GP van Nierop reports no disclosures.
J Klaasse reports no disclosures.
SMJ Scherbeijn reports no disclosures.
GMGM Verjans reports no disclosures.
AA Baltissen-van der Eijk reports no disclosures.
RQ Hintzen reports no disclosures.