Evidence map›Paper›PMID 33436735›Full record

ArticleScientific reports2021

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 and 33 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 3 pooled it
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 3 syntheses or guidelines pooled it, 33 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Review
  7. Article
  8. From lesion detection to outcome prediction: artificial intelligence and deep learning applications in multiple sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Review
  9. Review
  10. The epidemiology, pathology and pathogenesis of MS: Therapeutic implications.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  11. Article
  12. Article
  13. The Role of Gut Microbiota in Neuromyelitis Optica Spectrum Disorder.International journal of molecular sciences · 2024
    Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

43 authors at 20 institutions in 1 country.

Mitsuru WatanabeDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Yuri NakamuraDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Shinya SatoDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Masaaki NiinoDepartment of Clinical Research, National Hospital Organization Hokkaido Medical Center, 1-1, 5-7 Yamanote, Nishi-ku, Sapporo, 063-0005, Japan.
Hikoaki FukauraDepartment of Neurology, Saitama Medical Center, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan.
Masami TanakaMultiple Sclerosis Center, National Hospital Organization Utano National Hospital, 8 Ondoyama, Narutaki, Ukyo-ku, Kyoto, 616-8255, Japan.
Hirofumi OchiDepartment of Neurology and Geriatric Medicine, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.
Takashi KandaDepartment of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
Yukio TakeshitaDepartment of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
Takanori YokotaDepartment of Neurology and Neurological Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Yoichiro NishidaDepartment of Neurology and Neurological Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Makoto MatsuiDepartment of Neurology, Kanazawa Medical University, 1-1 Uchinada, Kahoku, Ishikawa, 920-0293, Japan.
Shigemi NagayamaDepartment of Neurology, Kanazawa Medical University, 1-1 Uchinada, Kahoku, Ishikawa, 920-0293, Japan.
Susumu KusunokiDepartment of Neurology, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
Katsuichi MiyamotoDepartment of Neurology, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
Masanori MizunoDivision of Neurology and Gerontology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidoori, Yahaba, Iwate, 028-3695, Japan.
Izumi KawachiDepartment of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-ku, Niigata, 951-8585, Japan.
Etsuji SajiDepartment of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-ku, Niigata, 951-8585, Japan.
Takashi OhashiDivision of Neurology, Department of Internal Medicine, Tokyo Women's Medical University Yachiyo Medical Center, 477-96 Owadashinden, Yachiyo, Chiba, 276-8524, Japan.
Shun ShimohamaDepartment of Neurology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan.
Shin HisaharaDepartment of Neurology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan.
Kazutoshi NishiyamaDepartment of Neurology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
Takahiro IizukaDepartment of Neurology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
Yuji NakatsujiDepartment of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Tatsusada OkunoDepartment of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Kazuhide OchiDepartment of Clinical Neuroscience and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Akio SuzumuraDepartment of Neurology, Kaikokai-Jousai Hospital, 1-4 Kitabatake, Nakamura-ku, Nagoya, 453-0815, Japan.
Ken YamamotoDepartment of Medical Biochemistry, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
Yuji KawanoDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Shoji TsujiDepartment of Neurology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Makoto HirataLaboratory of Rare Disease Resource Library, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7‑6‑8, Saito‑Asagi, Ibaraki, Osaka, 567‑0085, Japan.
Ryuichi SakateLaboratory of Rare Disease Resource Library, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7‑6‑8, Saito‑Asagi, Ibaraki, Osaka, 567‑0085, Japan.
Tomonori KimuraLaboratory of Rare Disease Resource Library, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7‑6‑8, Saito‑Asagi, Ibaraki, Osaka, 567‑0085, Japan.
Yuko ShimizuDepartment of Neurology, School of Medicine, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Akiko NagaishiDepartment of Neurology, National Hospital Organization Nagasaki Kawatana Medical Center, 2005-1 Shimogumigo, Kawatana-machi, Nagasaki, 859-3615, Japan.
Kazumasa OkadaDepartment of Neurology, University of Occupational and Environmental Health School of Medicine, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
Fumie HayashiDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Ayako SakodaDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Katsuhisa MasakiDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Koji ShinodaDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Noriko IsobeDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Takuya MatsushitaDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Jun-Ichi KiraDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. kira@neuro.med.kyushu-u.ac.jp.
Kyushu University · JPNational Institute of Biomedical Innovation, Health and Nutrition · JPFukuoka International University · JPKanazawa Medical University · JPKindai University · JPKitasato University · JPOsaka University · JPSapporo Medical University · JPTokyo Medical and Dental University · JPYamaguchi University · JPEhime University · JPHiroshima University · JPIwate Medical University · JPKurume University · JPNagasaki Kawatana Medical Center · JPNational Hospital Organization Hokkaido Medical Center · JPNiigata University · JPNiigata University Medical and Dental Hospital · JPSocial Insurance Saitama Chuo Hospital · JPThe University of Tokyo · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Biological Specimen BanksGenetic Association StudiesAdultCase-Control StudiesFemaleGenotypeHLA-DP beta-ChainsHLA-DRB1 ChainsHumansJapanMaleMiddle AgedMultiple SclerosisNeuromyelitis OpticaPhenotypeHLA-DPB1 antigenHLA-DP beta-ChainsHLA-DRB1 Chains

Identifiers

PMID33436735
PMCPMC7804194
OpenAlexW3119603177

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