Archivum Immunologiae et Therapiae Experimentalis

, Volume 58, Issue 5, pp 325–333

Autoimmune Versus Oligodendrogliopathy: The Pathogenesis of Multiple Sclerosis

Authors

    • Department of NeurologyKeio University School of Medicine
    • Department of AnatomyKeio University School of Medicine
    • Center for Integrated Medical ResearchKeio University School of Medicine
  • Sadakazu Aiso
    • Department of AnatomyKeio University School of Medicine
  • Norihiro Suzuki
    • Department of NeurologyKeio University School of Medicine
REVIEW

DOI: 10.1007/s00005-010-0094-x

Cite this article as:
Nakahara, J., Aiso, S. & Suzuki, N. Arch. Immunol. Ther. Exp. (2010) 58: 325. doi:10.1007/s00005-010-0094-x

Abstract

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS); it affect millions of patients worldwide and the number of patients is on the rise. Current treatment options are fairly limited and there is a strong unmet need for disease-targeted therapies for MS. The most widely accepted hypothesis for the pathogenesis of MS is that it is a primary autoimmune disease in which myelin-specific T cells play a central role in the progression of demyelination. According to this hypothesis, a powerful immune suppression or a reconstruction of the immune system to abrogate disease-specific leukocytes early in the development of the disease is expected to halt or even reverse the disease, since remyelination is an exceptionally efficient regenerative process in the CNS. However, recent neuropathological studies have provided evidence of primary oligodendrogliopathy as a cause of demyelination, suggesting that immune reactions may be a mere secondary event in the course of MS. On the other hand, some recent clinical trial results of new immune-suppressive treatments showed a nearly complete blockade of relapses and significant, albeit incomplete, neurological improvement. Therefore, which hypothesis—autoimmunity or oligodendrogliopathy—lights the correct path to a “cure” for MS?

Keywords

Multiple sclerosisPathogenesisAutoimmuneOligodendrogliopathy

Abbreviations

ADEM

Acute disseminating encephalomyelitis

BBB

Blood–brain barrier

CCL

CC chemokine ligand

CNS

Central nervous system

CSF

Cerebrospinal fluid

EAE

Experimental autoimmune encephalomyelitis

GA

Glatiramer acetate

IFN

Interferon

IL

Interleukin

LT

Lymphotoxin

MR

Magnetic resonance

MS

Multiple sclerosis

MTX

Mitoxantrone

OPCs

Oligodendrocyte precursor cells

PPMS

Primary progressive multiple sclerosis

RRMS

Relapsing-remitting multiple sclerosis

SAS

Subarachnoid space

SPMS

Secondary progressive multiple sclerosis

TNF

Tumor necrosis factor

Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2010