Multiple sclerosis: immunopathogenesis and controversies in defining the cause.
OBJECTIVE
Multiple sclerosis is a major cause of neurological disability in Western societies. The most important reason for the limited success obtained in the treatment and prevention so far is most likely related to the limited knowledge about its cause and pathogenesis. This paper discusses recent progress and controversies in the understanding of the pathogenesis and cause of multiple sclerosis.


RESULTS
Both T helper cells type 1 (Th1 cells), Th17 cells, cytotoxic T cells, B cells and regulatory T cells are involved in the inflammatory process. Axonal loss seems to be driven by inflammation during the early stages of disease but may become independent of inflammation at later stages. The target antigen of the immune response has not been identified. Weak genetic association has been established in two cytokine receptors, whereas increasing female: male ratio support the importance of environmental risk factors. A substantial proportion of intrathecal B cells are infected with Epstein-Barr virus.


CONCLUSIONS
Multiple sclerosis is a complex disease and calls for integrated efforts from immunology, epidemiology, neuroscience and genetics. In particular, the immunological implications of environmental risk factors such as vitamin D desufficiency, smoking and Epstein-Barr virus infection need to be explored.
Holmøy
Trygve
T
Institute of Immunology, Faculty of Medicine, Faculty Division Rikshospitalet, University of Oslo, Oslo, Norway. trygve.holmoy@rr-research.no
Hestvik
Anne Lise K
AL
D003141:Communicable Diseases / Q000150:complications; D004777:Environment; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007249:Inflammation; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012307:Risk Factors
D006649:Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell