Genetic and infectious profiles of Japanese multiple sclerosis patients.

Satoshi Yoshimura,Jun-Ichi Kira,Tomomi Yonekawa,Shinya Sato,Takuya Matsushita,Katsuhisa Masaki,Noriko Isobe,Ken Yamamoto,Yuji Kawano,Celia Oreja-Guevara

doi:10.1371/journal.pone.0048592

Abstract

BackgroundNationwide 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.Methodology/Principal FindingsWe 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.ConclusionsOur 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.

Highlights

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS)
Our study suggests that multiple sclerosis (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
Present study, we focused on HLA-DRB1 and -DPB1 loci that are associated with Japanese MS but not HLA class I, which have not shown any association with the disease

Summary

Introduction

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Neuromyelitis optica (NMO) is an inflammatory disease of the CNS selectively affecting the optic nerves and spinal cord. More than half of Asian OSMS patients do not have LESCLs, [9] and LESCLs are present in approximately one-fourth of patients with conventional MS (CMS), involving multiple sites of the CNS, including the cerebrum and cerebellum [10,11]. 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

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