Multiple sclerosis: Etiology and mechanism, with special reference to asians

Jun Ichi Kira

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Multiple sclerosis (MS) is a disease that targets myelin in the central nervous system (CNS). It is thought to be an autoimmune disease but this is not yet proven. Genome-wide association studies have revealed many susceptibility genes for MS, and the functions of these genes are mostly immune-related, supporting the autoimmune hypothesis. Increased numbers of T cells showing inter- and intramolecular epitope spreading against myelin proteins; increased cerebrospinal fluid (CSF) levels of interferon (IFN)-γ, interleukin (IL)-17, and downstream pro-inflammatory cytokines; exacerbation of disease following IFN-γ administration; and increased percentages of T helper (Th)1 cells secreting IFN-γ and of Th17 cells secreting IL-17 at relapse all support T-cell involvement in MS lesion formation. B-cell infiltration in the CNS parenchyma is not prominent, while B-cell follicles in the meninges appear to have a close correlation with subpial demyelination, suggesting an involvement of autoantibodies. However, no specific autoantibodies for MS have been detected, although anti-aquaporin-4 antibodies are a specific biomarker for neuromyelitis optica (NMO). We reported the extensive loss of connexins (Cxs) 43, 32, and 47 in acute lesions in patients with Baló‘s concentric sclerosis, MS, and NMO. Such loss of astroglial and oligodendroglial Cxs could induce widespread disruption of the glial syncytium, leading to failure of energy source transfer. Thus, loss of Cxs in acute MS lesions may contribute to extensive lesion formation. In the Japanese population, HLA-DRB1*0405 is the most common susceptibility allele for non-NMO MS. DRB1*0405 carriers comprise >40% of all Japanese MS patients, and this proportion is higher in younger generations. HLA-DRB1*0405-positive MS patients show characteristic features, such as younger age at onset, fewer brain lesions, fewer CSF IgG abnormalities, and a slower progression. The recent increase in the number of MS patients in this subgroup may explain the overall decrease in onset age, as shown by the fourth nationwide survey of Japanese MS patients. Therefore, changes in environmental factors may have increased susceptibility to MS in Japanese populations with certain genetic backgrounds.

Original languageEnglish
Title of host publicationNeuroimmunological Diseases
PublisherSpringer Japan
Pages73-103
Number of pages31
ISBN (Electronic)9784431555940
ISBN (Print)9784431555933
DOIs
Publication statusPublished - Jan 1 2016

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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