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

Abstract

BackgroundThe 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). MethodsA 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. ResultsCarriers 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 (rs = −0.484, p = .036), NWMV (rs = −0.593, p = .008), and NTV (rs = −0.572, p = .011), and positive correlations between disease duration and FLAIR (rs = 0.539, p = .017) and T1 lesion volumes (rs = 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. ConclusionsOur study suggests that distinct HLA-DRB1 alleles could differentially influence brain and lesion volumes over the disease course of MS.