Scientific Reports (Jan 2021)
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 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
Affiliations
- Mitsuru Watanabe
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
- Yuri Nakamura
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
- Shinya Sato
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
- Masaaki Niino
- Department of Clinical Research, National Hospital Organization Hokkaido Medical Center
- Hikoaki Fukaura
- Department of Neurology, Saitama Medical Center
- Masami Tanaka
- Multiple Sclerosis Center, National Hospital Organization Utano National Hospital
- Hirofumi Ochi
- Department of Neurology and Geriatric Medicine, Ehime University Graduate School of Medicine
- Takashi Kanda
- Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine
- Yukio Takeshita
- Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine
- Takanori Yokota
- Department of Neurology and Neurological Science, Tokyo Medical and Dental University
- Yoichiro Nishida
- Department of Neurology and Neurological Science, Tokyo Medical and Dental University
- Makoto Matsui
- Department of Neurology, Kanazawa Medical University
- Shigemi Nagayama
- Department of Neurology, Kanazawa Medical University
- Susumu Kusunoki
- Department of Neurology, Faculty of Medicine, Kindai University
- Katsuichi Miyamoto
- Department of Neurology, Faculty of Medicine, Kindai University
- Masanori Mizuno
- Division of Neurology and Gerontology, Department of Internal Medicine, Iwate Medical University
- Izumi Kawachi
- Department of Neurology, Brain Research Institute, Niigata University
- Etsuji Saji
- Department of Neurology, Brain Research Institute, Niigata University
- Takashi Ohashi
- Division of Neurology, Department of Internal Medicine, Tokyo Women’s Medical University Yachiyo Medical Center
- Shun Shimohama
- Department of Neurology, Sapporo Medical University School of Medicine
- Shin Hisahara
- Department of Neurology, Sapporo Medical University School of Medicine
- Kazutoshi Nishiyama
- Department of Neurology, Kitasato University School of Medicine
- Takahiro Iizuka
- Department of Neurology, Kitasato University School of Medicine
- Yuji Nakatsuji
- Department of Neurology, Osaka University Graduate School of Medicine
- Tatsusada Okuno
- Department of Neurology, Osaka University Graduate School of Medicine
- Kazuhide Ochi
- Department of Clinical Neuroscience and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University
- Akio Suzumura
- Department of Neurology, Kaikokai-Jousai Hospital
- Ken Yamamoto
- Department of Medical Biochemistry, Kurume University School of Medicine
- Yuji Kawano
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
- Shoji Tsuji
- Department of Neurology, Graduate School of Medicine, The University of Tokyo
- Makoto Hirata
- Laboratory of Rare Disease Resource Library, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition
- Ryuichi Sakate
- Laboratory of Rare Disease Resource Library, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition
- Tomonori Kimura
- Laboratory of Rare Disease Resource Library, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition
- Yuko Shimizu
- Department of Neurology, School of Medicine, Tokyo Women’s Medical University
- Akiko Nagaishi
- Department of Neurology, National Hospital Organization Nagasaki Kawatana Medical Center
- Kazumasa Okada
- Department of Neurology, University of Occupational and Environmental Health School of Medicine
- Fumie Hayashi
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
- Ayako Sakoda
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
- Katsuhisa Masaki
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
- Koji Shinoda
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
- Noriko Isobe
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
- Takuya Matsushita
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
- Jun-ichi Kira
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
- DOI
- https://doi.org/10.1038/s41598-020-79833-7
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 16
Abstract
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.
