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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.

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