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

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 ShimohamaShin 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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number607
JournalScientific reports
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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