Medline ® Abstracts for References 40,44

of 'Epidemiology and clinical features of multiple sclerosis in adults'

40
TI
Epstein-Barr virus in multiple sclerosis.
AU
Bagert BA
SO
Curr Neurol Neurosci Rep. 2009;9(5):405.
 
Recent seroepidemiologic and pathologic evidence suggests that prior infection with Epstein-Barr virus (EBV) may be necessary for the development of multiple sclerosis (MS). EBV infects more than 90% of all humans, most of whom remain healthy. In contrast, 99% of MS patients have evidence of prior infection with EBV. EBV infects resting B lymphocytes, immortalizing them into long-lived memory B cells that survive largely undetected by the immune system in the peripheral circulation. MS patients show elevated titers to EBV years before developing any neurologic symptoms. Postmortem pathologic analysis of brains of patients with MS has revealed diffuse EBV-associated B-cell dysregulation in all forms of MS. Theories of pathogenesis of EBV in MS include antigenic mimicry, immortalization of B-cell clones, and cytotoxic T-cell dysfunction against virally infected B cells. This article reviews the existing evidence of the relationship between EBV and MS and considers the therapeutic implication of this evidence.
AD
Department of Neurology, 1542 Tulane Avenue, Room 718B, Louisiana State University Health Science Center, New Orleans, LA 70112, USA. bbager@lsuhsc.edu
PMID
44
TI
Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain.
AU
Serafini B, Rosicarelli B, Franciotta D, Magliozzi R, Reynolds R, Cinque P, Andreoni L, Trivedi P, Salvetti M, Faggioni A, Aloisi F
SO
J Exp Med. 2007;204(12):2899.
 
Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, has been associated with multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS), but direct proof of its involvement in the disease is still missing. To test the idea that MS might result from perturbed EBV infection in the CNS, we investigated expression of EBV markers in postmortem brain tissue from MS cases with different clinical courses. Contrary to previous studies, we found evidence of EBV infection in a substantial proportion of brain-infiltrating B cells and plasma cells in nearly 100% of the MS cases examined (21 of 22), but not in other inflammatory neurological diseases. Ectopic B cell follicles forming in the cerebral meninges of some cases with secondary progressive MS were identified as major sites of EBV persistence. Expression of viral latent proteins was regularly observed in MS brains, whereas viral reactivation appeared restricted to ectopic B cell follicles and acute lesions. Activation of CD8+ T cells with signs of cytotoxicity toward plasma cells was also noted at sites of major accumulations of EBV-infected cells. Whether homing of EBV-infected B cells to the CNS is a primary event in MS development or the consequence of a still unknown disease-related process, we interpret these findings as evidence that EBV persistence and reactivation in the CNS play an important role in MS immunopathology.
AD
Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.
PMID