Abstract: HHV6 IgG Response and Genetic Factor rs11154801 Associate With Relapse Rate in Children (The 27th Annual Meeting of the CMSC and the 5th Cooperative Meeting of the CMSC-ACTRIMS)

Saturday, June 1, 2013

Jennifer Graves, MD, PhD , Neurology, University of California, San Francisco, San Francisco, CA

Lisa Barcellos, PhD , Public Health, Genetic Epidemiology, University of California, Berkeley, Berkeley, CA

Lauren Krupp, MD , Neurology, Stony Brook University Medical Center, East Setauket, NY

Anita L Belman, MD , Neurology, Stony Brook University Medical Center, East Setauket, NY

Judith A James, MD , Rheumatology, Oklahoma Medical Research Foundation, University of Oklahoma, Oklahoma City, OK

Emmanuelle Waubant, MD, PhD , Neurology, University of California, San Francisco, San Francisco, CA

Background: While exposures to common herpes viruses and genetic polymorphisms have been identified as susceptibility factors for MS, their effects on disease course in adults or children are unclear. Pediatric MS patients are an ideal population for study, as higher risk factor burden may result in earlier MS onset.

Objectives: We sought to determine the associations of previously identified viral and genetic susceptibility factors with relapse rate in pediatric multiple sclerosis (MS).

Methods: Batched ELISA IgG assays for antibody responses against EBV, CMV and HSV-1and 2 and IgG immunofluorescence assay (Biocell) for HHV6A were performed for MS or clinically isolated syndrome patients from two Pediatric MS Centers. Genotyping was performed on the Illumina 660K platform. The top 10 single nucleotide polymorphisms (SNPs) associated with MS risk in adult genome wide association studies were evaluated for association with relapse rate. The SNPs were ranked by p value. Weighted scores of the top 52 SNPs and HLA-DRB1*1501 were also evaluated. Repeated events models adjusted for disease-modifying therapy, demographic variables, and vitamin D level.

Results: For 171 subjects, 416 relapse events were captured over 516 patient-years of follow-up. HHV6 responses in the highest quartile were associated with increased hazard for relapse compared to lower response levels (HR 1.54; 95% CI 1.15, 2.05; p=0.003). This effect was modified by absence (HR 1.68, 95% CI 1.25, 2.27, p=0.001) vs. presence (HR 1.04, 95% CI : 0.66, 1.64, p=0.87) of HLA-DRB1*1501. No association with relapse rate was seen for EBV (EBNA1), CMV, or HSV-1. Analysis of HSV-2 is in progress. Having 2 copies of risk allele for SNP rs11154801 [Abelson helper integration site 1 (AHI1)] was associated with higher relapse rate (HR 2.22, 95%CI 1.52-3.25, p<0.001) compared to absence of risk allele. We found no association between weighted genetic risk scores or HLA-DRB1*1501 and relapse hazard rate.

Conclusions: Elevated HHV6 IgG responses and the MS risk allele for AHI1 may be associated with higher relapse rates in children. Replication of these results is required.

P48 HHV6 IgG Response and Genetic Factor rs11154801 Associate With Relapse Rate in Children