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Multiple Sclerosis: Autoimmune Disease or Autoimmune Reaction?

Published online by Cambridge University Press:  02 December 2014

Peter K. Stys
Peter K. Stys*
Affiliation:
Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
*
Department of Clinical Neurosciences, HRIC 1AA22, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada. E-mail: pstys@ucalgary.ca
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Abstract:

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Multiple sclerosis (MS) is traditionally considered an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) with much knowledge available to support this view. However, this characterization implies that the primary event is an aberrant immune response directed at CNS antigens, promoting inflammation and later driving progressive axo-glial degeneration. Trials with potent anti-inflammatory agents and detailed neuropathological studies raise questions about this sequence of events. This hypothetical paper argues that MS may be primarily a “cytodegenerative” disease, possibly first involving the oligodendrocyte/myelin unit. Liberation of autoantigens secondarily recruits an immune response, the force of which heavily depends on the host's immune predisposition. Thus, the spectrum of MS from highly aggressive Marburg type, to primary progressive disease with little inflammatory burden, is governed by a “convolution” between the underlying cytodegeneration and the host's immune predilection. Clinical heterogeneity may be a reflection of a variable immune response, whereas in reality, the “real MS” may be a homogeneous degenerative process analogous to well known primary neurodegenerative diseases.

Résumé:

RÉSUMÉ:

La sclérose en plaques (SP) est considérée traditionnellement comme une maladie démyélinisante inflammatoire auto–immune du système nerveux central (SNC), une notion bien étayée par de vastes connaissances. Cependant, cette interprétation implique que l'événement primaire est une réponse immunitaire aberrante dirigée contre des antigènes du SNC, qui favorise l'inflammation et subséquemment la dégénérescence axo–gliale progressive. Des essais au moyen d'agents anti–inflammatoires puissants et des études neuropathologiques détaillées soulèvent des questions au sujet de cette succession d'événements. Dans cet article, nous émettons l'hypothèse que la SP puisse être principalement une maladie “cytodégénérative”, impliquant possiblement au départ l'unité oligodendrocyte/myéline. La libération d'auto–antigènes recruterait secondairement une réponse immunitaire dont la force dépendrait principalement de la prédisposition immunitaire de l'hôte. Ainsi, le spectre de la SP, de la forme très agressive de Marburg à la forme progressive primaire dont le fardeau inflammatoire est minime, serait régi par une “convolution” entre la cytodégénérescence sous–jacente et la prédisposition immunitaire de l'hôte. L'hétérogénéité clinique pourrait être le reflet d'une réponse immunitaire variable, alors qu'en réalité, la “vraie SP” pourrait être un processus dégénératif homogène analogue à celui des maladies neurodégénératives primaires bien connues.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 37 , supplement S2 , September 2010 , pp. S16 - S23
Copyright
Copyright © Canadian Neurological Sciences Federation 2010

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