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Infection and multiple sclerosis
  1. B Anlar
  1. Department of Pediatric Neurology, Hacettepe University, Ankara 06100, Turkey; banlar{at}

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    The article by Hawkes1 and the editorial commentary about the role of infectious agents in multiple sclerosis (MS) examined this question from a new viewpoint based on epidemiological observations.2 Several infectious agents, most not sexually transmitted, were reported to be associated with MS according to epidemiological data, serology in CSF and blood, or demonstration of pathogens in tissue. A relation with measles virus (MV) has been an early and most consistent finding. More recently, higher prevalence and higher titres of antibodies against human herpesvirus 6 (HHV6), but not other herpesviruses, were shown in MS patients compared to control groups, suggesting different exposure to HHV6 in MS.3 HHV6, like vaccine strain MV and certain wild type MV, uses the membrane cofactor protein (MCP; CD46) as a receptor for entry into cells. This suggests a possible involvement of CD46 in MS.

    The possibility of a particular isoform of CD46 predisposing MS patients to infection is unlikely because all isoforms have similar affinity to MV. Increased levels of soluble CD46 have been reported in the serum and cerebrospinal fluid of MS patients, more in those who have HHV6 DNA.4 One interpretation of these findings involved increased activity of the complement system in MS. However, experimental studies show no influence of inflammatory cytokines on CD46 expression and do not support inflammation as a cause of increased CD46.5 Incorporation of CD46 in the viral envelope, or a possible genetic propensity in MS patients, have also been considered as causes of increased CD46.4 While its origin in MS is unclear, soluble CD46 might be involved in viral pathogenesis by binding the virus in the viraemic phase and allowing another to attach to CD46 and spread from cell to cell. Both HHV6 and MV are infectious agents encountered in early childhood, and HHV6 can indeed become reactivated a few weeks after primary MV infection. On the other hand, because HHV6 and MV downregulate CD46 expression on the infected cell, they may diminish the entry of each other, delaying the time of infection. Therefore, they might produce increased antibody levels in young adults through delayed infection with, or reactivation of, each other. These suggest increased antibodies against these two viruses in MS may be interrelated.

    The question remains whether a cause-effect relation exists between infectious organisms and MS, or whether viruses are just a consequence of the activation of the inflammatory-immune sequence or increased susceptibility of MS patients to infection. Studies of CD46 and other viral receptors seem warranted in MS.


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