SHIMIZU Yuko    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data
Journal	Formal name：Scientific Reports Abbreviation：Sci Rep ISSN code：20452322
Domestic / Foregin	Foregin
Volume, Issue, Page	11(1),pp.607
Author and coauthor	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
Publication date	2021/01/12
Summary	LA 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.
DOI	10.1038/s41598-020-79833-
PMID	33436735