Abstract
Multiple sclerosis (MS) is considered to be an autoimmune, inflammatory disease of the CNS. In most patients, the disease follows a relapsing-remitting course and is characterized by dynamic inflammatory demyelinating lesions in the CNS. Although on the surface MS may appear consistent with a primary autoimmune disease, questions have been raised as to whether inflammation and/or autoimmunity are really at the root of the disease, and it has been proposed that MS might in fact be a degenerative disorder. We argue that MS may be an 'immunological convolution' between an underlying primary degenerative disorder and the host's aberrant immune response. To better understand this disease, we might need to consider non-inflammatory primary progressive MS as the 'real' MS, with inflammatory forms reflecting secondary, albeit very important, reactions.
Highlights
Abstract | Multiple sclerosis (MS) is considered to be an autoimmune, inflammatory disease of the CNS
Immunochemical studies on early MS lesions corroborate these observations, as they show preferential loss of myelin-associated glycoprotein, an adhesion molecule expressed on the inner periaxonal wraps of myelin[11]; if an extrinsic immune cell- or antibody-mediated attack were primarily responsible for such early changes, one would not expect these changes to occur in the innermost myelin regions
The reasonable question that was raised was whether such secondary inflammation could feed back and promote further degeneration, completing an analogous ‘inside-out’ cycle as we propose for multiple sclerosis (MS) (FIG. 1)
Summary
P., Zamponi, G., van Minnen, J. and Geurts, J. (2012). Will the real multiple sclerosis please stand up?. We argue that MS may be an ‘immunological convolution’ between an underlying primary degenerative disorder and the host’s aberrant immune response To better understand this disease, we might need to consider non-inflammatory primary progressive MS as the ‘real’ MS, with inflammatory forms reflecting secondary, albeit very important, reactions. Strong genetic associations with immune regulation have been uncovered[4], mechanisms of immune attack against CNS elements elucidated[5] and pharmacological agents developed, all aimed at modulating the immune system[6] This approach, based on the overwhelming evidence that the disease has an inflammatory phenotype, rests on the assumption that the pathophysiology begins with an immune dysregulation — that is, it is based on an ‘outside‐in’ model of MS We speculate on some of the possible non-immune molecular targets that may be dysregulated in MS, the study of which may lead us closer to an understanding of its root cause
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
