Papers

International journal
Jan 12, 2021

HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data.

Scientific reports
  • Mitsuru Watanabe
  • Yuri Nakamura
  • Shinya Sato
  • Masaaki Niino
  • Hikoaki Fukaura
  • Masami Tanaka
  • Hirofumi Ochi
  • Takashi Kanda
  • Yukio Takeshita
  • Takanori Yokota
  • Yoichiro Nishida
  • Makoto Matsui
  • Shigemi Nagayama
  • Susumu Kusunoki
  • Katsuichi Miyamoto
  • Masanori Mizuno
  • Izumi Kawachi
  • Etsuji Saji
  • Takashi Ohashi
  • Shun Shimohama
  • Shin Hisahara
  • Kazutoshi Nishiyama
  • Takahiro Iizuka
  • Yuji Nakatsuji
  • Tatsusada Okuno
  • Kazuhide Ochi
  • Akio Suzumura
  • Ken Yamamoto
  • Yuji Kawano
  • Shoji Tsuji
  • Makoto Hirata
  • Ryuichi Sakate
  • Tomonori Kimura
  • Yuko Shimizu
  • Akiko Nagaishi
  • Kazumasa Okada
  • Fumie Hayashi
  • Ayako Sakoda
  • Katsuhisa Masaki
  • Koji Shinoda
  • Noriko Isobe
  • Takuya Matsushita
  • Jun-Ichi Kira
  • Display all

Volume
11
Number
1
First page
607
Last page
607
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1038/s41598-020-79833-7

HLA genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied HLA-DRB1/DPB1 genotype-phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS/NMOSD Biobank materials. HLA-DRB1*04:05, DRB1*15:01 and DPB1*03:01 correlated with MS susceptibility and DRB1*01:01, DRB1*09:01, DRB1*13:02 and DPB1*04:01 were protective against MS. HLA-DRB1*15:01 was associated with increased optic neuritis and cerebellar involvement and worsened visual and pyramidal functional scale (FS) scores, resulting in higher progression index values. HLA-DRB1*04:05 was associated with younger onset age, high visual FS scores, and a high tendency to develop optic neuritis. HLA-DPB1*03:01 increased brainstem and cerebellar FS scores. By contrast, HLA-DRB1*01:01 decreased spinal cord involvement and sensory FS scores, HLA-DRB1*09:01 decreased annualized relapse rate, brainstem involvement and bowel and bladder FS scores, and HLA-DRB1*13:02 decreased spinal cord and brainstem involvement. In NMOSD, HLA-DRB1*08:02 and DPB1*05:01 were associated with susceptibility and DRB1*09:01 was protective. Multivariable analysis revealed old onset age, long disease duration, and many relapses as independent disability risks in both MS and NMOSD, and HLA-DRB1*15:01 as an independent risk only in MS. Therefore, both susceptibility and protective alleles can influence the clinical manifestations in MS, while such genotype-phenotype correlations are unclear in NMOSD.

Link information
DOI
https://doi.org/10.1038/s41598-020-79833-7
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33436735
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804194
ID information
  • DOI : 10.1038/s41598-020-79833-7
  • Pubmed ID : 33436735
  • Pubmed Central ID : PMC7804194

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