Genetic loci for Epstein-Barr virus nuclear antigen-1 are associated with risk of multiple sclerosis.

BACKGROUND: Infection with the Epstein-Barr virus (EBV) is associated with an increased risk of multiple sclerosis (MS). OBJECTIVE: We sought genetic loci influencing EBV nuclear antigen-1 (EBNA-1) IgG titers and hypothesized that they may play a role in MS risk. METHODS: We performed a genome-wide association study (GWAS) of anti-EBNA-1 IgG titers in 3599 individuals from an unselected twin family cohort, followed by a meta-analysis with data from an independent EBNA-1 GWAS. We then examined the shared polygenic risk between the EBNA-1 GWAS (effective sample size (Neff) = 5555) and a large MS GWAS (Neff = 15,231). RESULTS: We identified one locus of strong association within the human leukocyte antigen (HLA) region, of which the most significantly associated genotyped single nucleotide polymorphism (SNP) was rs2516049 (p = 4.11 × 10-9). A meta-analysis including data from another EBNA-1 GWAS in a cohort of Mexican-American families confirmed that rs2516049 remained the most significantly associated SNP (p = 3.32 × 10-20). By examining the shared polygenic risk, we show that the genetic risk for elevated anti-EBNA-1 titers is positively correlated with the development of MS, and that elevated EBNA-1 titers are not an epiphenomena secondary to MS. In the joint meta-analysis of EBNA-1 titers and MS, loci at 1p22.1, 3p24.1, 3q13.33, and 10p15.1 reached genome-wide significance (p < 5 × 10-8). CONCLUSIONS: Our results suggest that apart from the confirmed HLA region, the association of anti-EBNA-1 IgG titer with MS risk is also mediated through non-HLA genes, and that studies aimed at identifying genetic loci influencing EBNA immune response provides a novel opportunity to identify new and characterize existing genetic risk factors for MS.

Design and operation of an automated high-throughput monoclonal antibody facility.

Monoclonal antibodies now form a key part of the biochemist's toolbox, and are important reagents for therapeutic applications. This has resulted in a need for high-throughput production to satisfy the demand from the global community. Manual production involves overwhelming amounts of tissue culture and associated liquid handling steps to achieve high-throughput operation. By contrast, automated systems can readily cope with the numbers required. In this review, we address the development of automated systems, and discuss the pros and cons of their operation.