Genetic and environmental factors underlying the rapid changes in epidemiological and clinical features of multiple sclerosis and neuromyelitis optica in Japanese

Jun Ichi Kira

Research output: Contribution to journalReview articlepeer-review

7 Citations (Scopus)

Abstract

The discovery of a specific biomarker for neuromyelitis optica (NMO), NMO-immunoglobulin G (IgG)/anti-aquaporin-4 (AQP4) antibody, requires us to take it into account when interpreting epidemiological findings on multiple sclerosis (MS). Recent genetic studies showed that HLA-DRB1*0405 is the most common susceptibility allele for non-NMO MS in Japanese, and that DRB1*0405 carriers comprise >40% of all Japanese MS patients. Thus, idiopathic central nervous system demyelinating disease in Japanese can be subclassified into DRB1*0405-positive and -negative MS, and anti-AQP4 antibody-positive and -negative NMO. HLA-DRB1*0405-positive MS patients show younger age at onset, fewer brain lesions and a slower progression. The recent increase in the numbers of MS patients in this subgroup could explain the decrease in age at onset, as shown by the fourth nationwide survey in Japanese MS patients. Among HLA-DRB1*0405-negative MS patients, DRB1*1501 is a risk factor for MS, and DRB1*1501 carriers have high frequencies of brain lesions fulfilling the Barkhof criteria and cerebrospinal fluid IgG abnormalities. HLA-DRB1*0405-negative MS patients have higher frequencies of Epstein-Barr virus infection, but a lower frequency of Helicobacter pylori infection, which reflects improved sanitation in childhood. Anti-AQP4 antibody-positive NMO is associated with H. pylori and Chlamydia pneumoniae infections. The effects of improved sanitation on this subgroup might explain the decrease in incidence of opticospinal MS with longitudinally extensive spinal cord lesions, regarded as the same disease as NMO, as suggested by the fourth nationwide survey. Therefore, changes in environmental factors could have differentially influenced susceptibility to each disease subtype in Japanese.

Original languageEnglish
Pages (from-to)261-273
Number of pages13
JournalClinical and Experimental Neuroimmunology
Volume4
Issue number3
DOIs
Publication statusPublished - Dec 2013

All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Immunology
  • Immunology and Microbiology (miscellaneous)
  • Clinical Neurology

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