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We studied <jats:italic>HLA-DRB1\/DPB1<\/jats:italic> genotype\u2013phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS\/NMOSD Biobank materials. <jats:italic>HLA-DRB1*04:05<\/jats:italic>, <jats:italic>DRB1*15:01<\/jats:italic> and <jats:italic>DPB1*03:01<\/jats:italic> correlated with MS susceptibility and <jats:italic>DRB1*01:01<\/jats:italic>, <jats:italic>DRB1*09:01<\/jats:italic>, <jats:italic>DRB1*13:02<\/jats:italic> and <jats:italic>DPB1*04:01<\/jats:italic> were protective against MS. <jats:italic>HLA-DRB1*15:01<\/jats:italic> was associated with increased optic neuritis and cerebellar involvement and worsened visual and pyramidal functional scale (FS) scores, resulting in higher progression index values. <jats:italic>HLA-DRB1*04:05<\/jats:italic> was associated with younger onset age, high visual FS scores, and a high tendency to develop optic neuritis. <jats:italic>HLA-DPB1*03:01<\/jats:italic> increased brainstem and cerebellar FS scores. By contrast, <jats:italic>HLA-DRB1*01:01<\/jats:italic> decreased spinal cord involvement and sensory FS scores, <jats:italic>HLA-DRB1*09:01<\/jats:italic> decreased annualized relapse rate, brainstem involvement and bowel and bladder FS scores, and <jats:italic>HLA-DRB1*13:02<\/jats:italic> decreased spinal cord and brainstem involvement. In NMOSD, <jats:italic>HLA-DRB1*08:02<\/jats:italic> and <jats:italic>DPB1*05:01<\/jats:italic> were associated with susceptibility and <jats:italic>DRB1*09:01<\/jats:italic> was protective. Multivariable analysis revealed old onset age, long disease duration, and many relapses as independent disability risks in both MS and NMOSD, and <jats:italic>HLA-DRB1*15:01<\/jats:italic> as an independent risk only in MS. Therefore, both susceptibility and protective alleles can influence the clinical manifestations in MS, while such genotype\u2013phenotype correlations are unclear in NMOSD.<\/jats:p>","DOI":"10.1038\/s41598-020-79833-7","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T19:24:12Z","timestamp":1610479452000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS\/NMOSD Biobank 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Y. Nakamura received a grant and salary from Mitsubishi Tanabe Pharma, Bayer Yakuhin, Ltd., and the Japan Blood Products Organization, received speaker honoraria from Novartis Pharma and received a grant from JSPS KAKENHI (Grant Nos. 18H06214 and 19K21317). M.N. received consultancy fees, speaking fees and\/or honoraria from Novartis Pharma, Mitsubishi Tanabe Pharma, the Takeda Pharmaceutical Company, and Biogen Japan. M. Tanaka received speaker honoraria from Biogen Idec Japan, Takeda Pharma, Novartis Pharma, Eisai and Mitsubishi Tanabe Pharma, and served on the scientific advisory board for Biogen Idec Japan. H.O. is a scientific advisory board member of Biogen Japan and Novartis Pharma, and has received honoraria from Biogen Japan, Novartis Pharma, Mitsubishi Tanabe Pharma, and the Takeda Pharmaceutical Company. I.K. received a grant from JSPS KAKENHI (Grant No. 17K09776), funding for research, travel and\/or speaker honoraria from Novartis Pharma, Biogen, Alexion Pharmaceuticals, Bristol-Myers Squibb, Bayer Yakuhin Limited, Mitsubishi Tanabe Pharma, the Takeda Pharmaceutical Company, the Japan Blood Products Organization, Teijin Pharma and Astellas Pharma, and is a scientific advisory board member for Biogen, Novartis Pharma, the Takeda Pharmaceutical Company and Alexion Pharmaceuticals. E.S. received a grant from JSPS KAKENHI (Grant No. 18K15443). T. Ohashi received speaker honoraria from Biogen Japan, Novartis Pharma and the Takeda Pharmaceutical Company. T.I. received a grant from The Japan Epilepsy Research Foundation and research support from Astellas Pharma Inc. Y. Kawano received a grant from JSPS KAKENHI (Grant No. 19K07997). Y.S. received speaker honoraria and consultant fees from Bayer Yakuhin, Biogen Idec Japan, the Takeda Pharmaceutical Company, and Novartis Pharma. K.S. received speaker honoraria from Biogen Idec Japan and the Takeda Pharmaceutical Company. A. Sakoda received grant support from Yazuya. N.I. received grant support from Mitsubishi Tanabe Pharma, Osoegawa Neurology Clinic, Bayer Yakuhin, Ltd., and Japan Blood Products Organization, and received a research grant from JSPS KAKENHI (Grant No. 18K07529). T.M. received speaker honoraria payments from Mitsubishi Tanabe Pharma, Takeda Pharmaceutical Company, and Biogen Japan, and received a research grant from JSPS KAKENHI (Grant No. 20K07869). J.K. received consultant fees, speaking fees and\/or honoraria from Novartis Pharma, Mitsubishi Tanabe Pharma, Boehringer Ingelheim, Teijin Pharma, Takeda Pharmaceutical Company, Otsuka Pharmaceutical, Astellas Pharma, Pfizer Japan, Sumitomo Dainippon Pharma, and Eisai, and is supported by grants from JSPS KAKENHI (Grant Nos. 16H02657 and 19H01045), the Japan Agency for Medical Research and Development (AMED) (JP16ek0109039) and Health and Labour Sciences Research Grants on Intractable Diseases (H23-Nanchi-Ippan-017; H26-Nanchitou (Nan)-Ippan-074; H26-Itaku (Nan)-Ippan-050; H29-Nanchitou (Nan)-Ippan-043) and a Health and Labour Sciences Research Grant on Intractable Diseases (Neuroimmunological Diseases) (20FC1030).\u00a0The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"607"}}