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

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-DRB104:05, DRB115:01 and DPB103:01 correlated with MS susceptibility and DRB101:01, DRB109:01, DRB113:02 and DPB104:01 were protective against MS. HLA-DRB115:01 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-DRB104:05 was associated with younger onset age, high visual FS scores, and a high tendency to develop optic neuritis. HLA-DPB103:01 increased brainstem and cerebellar FS scores. By contrast, HLA-DRB101:01 decreased spinal cord involvement and sensory FS scores, HLA-DRB109:01 decreased annualized relapse rate, brainstem involvement and bowel and bladder FS scores, and HLA-DRB113:02 decreased spinal cord and brainstem involvement. In NMOSD, HLA-DRB108:02 and DPB105:01 were associated with susceptibility and DRB109:01 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.