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

<jats:title>Abstract</jats:title><jats:p><jats:italic>HLA</jats:italic> genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied <jats:italic>HLA-DRB1/DPB1</jats:italic> genotype–phenotype 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–phenotype correlations are unclear in NMOSD.</jats:p>