title: Genetic and infectious profiles of Japanese multiple sclerosis patients.
abstract: BACKGROUND
  Nationwide surveys conducted in Japan over the past thirty years have revealed a four-fold increase in the estimated number of multiple sclerosis (MS) patients, a decrease in the age at onset, and successive increases in patients with conventional MS, which shows an involvement of multiple sites in the central nervous system, including the cerebrum and cerebellum. We aimed to clarify whether genetic and infectious backgrounds correlate to distinct disease phenotypes of MS in Japanese patients.
  
  
  RESULTS
  We analyzed HLA-DRB1 and -DPB1 alleles, and IgG antibodies specific for Helicobacter pylori, Chlamydia pneumoniae, varicella zoster virus, and Epstein-Barr virus nuclear antigen (EBNA) in 145 MS patients and 367 healthy controls (HCs). Frequencies of DRB1*0405 and DPB1*0301 were significantly higher, and DRB1*0901 and DPB1*0401 significantly lower, in MS patients as compared with HCs. MS patients with DRB1*0405 had a significantly earlier age of onset and lower Progression Index than patients without this allele. The proportion and absolute number of patients with DRB1*0405 successively increased with advancing year of birth. In MS patients without DRB1*0405, the frequency of the DRB1*1501 allele was significantly higher, while the DRB1*0901 allele was significantly lower, compared with HCs. Furthermore, DRB1*0405-negative MS patients were significantly more likely to be positive for EBNA antibodies compared with HCs.
  
  
  CONCLUSIONS
  Our study suggests that MS patients harboring DRB1*0405, a genetic risk factor for MS in the Japanese population, have a younger age at onset and a relatively benign disease course, while DRB1*0405-negative MS patients have features similar to Western-type MS in terms of association with Epstein-Barr virus infection and DRB1*1501. The recent increase of MS in young Japanese people may be caused, in part, by an increase in DRB1*0405-positive MS patients.
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Noriko
authors.initials: N
authors.lastname: Isobe
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yonekawa
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsushita
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Masaki
authors.forename: Shinya
authors.initials: S
authors.lastname: Sato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kawano
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kira
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000906:Antibodies / Q000276:immunology; D051401:Aquaporin 4 / Q000276:immunology; D044466:Asian People; D016022:Case-Control Studies; D016993:Chlamydophila pneumoniae / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D059868:HLA-DP beta-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D016480:Helicobacter pylori / Q000276:immunology; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000209:etiology*; D010641:Phenotype; D055815:Young Adult
chemical_list: D000906:Antibodies; D051401:Aquaporin 4; D019309:Epstein-Barr Virus Nuclear Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D059811:HLA-DRB1 Chains