UBC Theses and Dissertations
Epstein-Barr virus infection and its lifelong autoimmune ramifications in developed and developing nations Jafari-Minab, Rana
Background. Epstein-Barr virus (EBV) infection is a major cause of malignancy worldwide. Maternal antibodies are thought to prevent EBV infection because infection is uncommon in early infancy. Additionally, maternal HIV infection is associated with an increased incidence of EBV infection in exposed infants possibly resulting from impaired transfer of EBV maternal antibodies. EBV, possibly in its acute form manifesting as infectious mononucleosis (IM), is also the highest environmental risk factor for the development of multiple sclerosis (MS), a devastating neurologic disease caused by autoimmune destruction of myelin. IM can be diagnosed by the presence of heterophile antibodies which target an antigen that is akin to certain myelin glycans in the brain. We hypothesized that maternal antibodies can protect against EBV acquisition by studying infants with and without maternal HIV exposure. Furthermore, , since the degeneration of myelin is a hallmark of MS, we hypothesized that EBV infection, specifically IM, primes the immune system to cross-react and attack myelin. Methods. Ugandan infants were followed for EBV acquisition from birth and measured antibody binding to EBV glycoproteins involved in B cell and epithelial cell entry, as well as viral neutralization and antibody-dependent cellular cytotoxicity (ADCC). Serum antibodies against major brain glycans were measured using a Luminex based glycan array for 6 infant samples (pre-post EBV infection) and 9 adults with IM. Results. HIV-exposed uninfected infants had significantly higher titers than HIV-unexposed uninfected infants for all EBV-binding and neutralizing antibodies measured (p<0.01), but not ADCC activity, which was similar between groups. No antibody measure was associated with a decreased risk of EBV acquisition in the cohort. IM-positive sera had 10 times the anti-glycan antibodies to major brain glycans compared to pre and post-EBV infected infants, while there was no significant difference between pre-post EBV infected infant samples. Conclusions. Our findings indicate that in this cohort maternal antibody did not protect infants against EBV infection through viral neutralization. The increase in anti-myelin antibodies in individuals with IM suggests that the development of cross-reactivity towards myelin may be a mechanistic link between IM and MS.
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