Risk HLA-DRB1 alleles differentially influence brain and lesion volumes in Japanese patients with multiple sclerosis

Background: The effects of distinct HLA alleles on the brain and lesion volumes remain to be established, particularly in non-Caucasian populations. Two distinct susceptibility alleles, DRB1*15:01 and DRB1*04:05, are prevalent in the Japanese population; we therefore aimed to clarify the effects of HLA-DRB1 alleles on brain and lesion volumes in multiple sclerosis (MS). Methods: A total of 66 patients with MS (50 relapsing remitting, 16 progressive) underwent brain MRI volumetry measuring fluid-attenuated inversion recovery (FLAIR) and T1 lesion volumes, and normalized whole-brain (NWBV), white matter (NWMV), gray matter (NGMV), cortical gray matter (NCGMV), deep gray matter (NDGMV) and thalamus (NTV) volumes, and HLA-DRB1 genotyping. Results: Carriers of HLA-DRB1*15:01(+)*04:05(−) and HLA-DRB1*15:01(−)*04:05(+) comprised 25.8% and 31.8% of patients, respectively. HLA-DRB1*15:01 carriers showed negative correlations between disease duration and NWBV (r_s = −0.484, p = .036), NWMV (r_s = −0.593, p = .008), and NTV (r_s = −0.572, p = .011), and positive correlations between disease duration and FLAIR (r_s = 0.539, p = .017) and T1 lesion volumes (r_s = 0.545, p = .016). By contrast, no significant correlation of any MRI parameters with disease duration was found in HLA-DRB1*04:05 carriers. HLA-DRB1*15:01 carriers had a significantly faster reduction in NWBV and NWMV by disease duration and smaller NDGMV than DRB1*15:01 non-carriers, whereas HLA-DRB1*04:05 carriers had a significantly slower increase in FLAIR and T1 lesion volumes than HLA-DRB1*04:05 non-carriers. Conclusions: Our study suggests that distinct HLA-DRB1 alleles could differentially influence brain and lesion volumes over the disease course of MS.