Despite a century of intensive investigation, the underlying cause of
multiple sclerosis has eluded us. It is clear that there exists a
prominent progressive degenerative phenotype together with an important
autoimmune inflammatory component, and careful histopathological
examination always shows, to a greater or lesser degree, concomitant
degeneration/demyelination and adaptive T cell-dependent immune
responses. Given this picture, it is difficult, if not impossible, to
definitively say whether degeneration or autoimmunity is the initiator
of the disease. In this review, I put forward the evidence for and
against both models and speculate that, in contrast to the accepted
view, it is equally likely that multiple sclerosis may be a degenerative
disease that secondarily elicits an autoimmune response, and suggest
how this might influence therapeutic approaches.
multiple sclerosis has eluded us. It is clear that there exists a
prominent progressive degenerative phenotype together with an important
autoimmune inflammatory component, and careful histopathological
examination always shows, to a greater or lesser degree, concomitant
degeneration/demyelination and adaptive T cell-dependent immune
responses. Given this picture, it is difficult, if not impossible, to
definitively say whether degeneration or autoimmunity is the initiator
of the disease. In this review, I put forward the evidence for and
against both models and speculate that, in contrast to the accepted
view, it is equally likely that multiple sclerosis may be a degenerative
disease that secondarily elicits an autoimmune response, and suggest
how this might influence therapeutic approaches.
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