TY - JOUR
T1 - Risk HLA-DRB1 alleles differentially influence brain and lesion volumes in Japanese patients with multiple sclerosis
AU - Fukumoto, Shoko
AU - Nakamura, Yuri
AU - Watanabe, Mitsuru
AU - Isobe, Noriko
AU - Matsushita, Takuya
AU - Sakoda, Ayako
AU - Hiwatashi, Akio
AU - Shinoda, Koji
AU - Yamasaki, Ryo
AU - Tsujino, Akira
AU - Kira, Jun ichi
N1 - Funding Information:
Dr. Fukumoto, Dr. Hiwatashi, and Dr. Yamasaki declare no conflicts of interest. Dr. Nakamura received grant support from Mitsubishi Tanabe Pharma, Bayer Yakuhin, Ltd., and Japan Blood Products Organization, and received speaker honoraria from Novartis Pharma. Dr. Watanabe received speaker honoraria and consultant fees from Novartis Pharma. Dr. Matsushita received speaker honoraria payments from Mitsubishi Tanabe Pharma, Takeda Pharmaceutical Company, and Biogen Japan. Dr. Isobe received grant support from Mitsubishi Tanabe Pharma, Osoegawa Neurology Clinic, Bayer Yakuhin, Ltd., and Japan Blood Products Organization. Dr. Kira received consultant fees, speaking fees and/or honoraria from Novartis Pharma, Mitsubishi Tanabe Pharma, Boehringer Ingelheim, Teijin Pharma, Takeda Pharmaceutical Company, Otsuka Pharmaceutical, Astellas Pharma, Pfizer Japan, Sumitomo Dainippon Pharma, and Eisai.
Funding Information:
This study was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI [grant numbers JP19H01045 , JP18K07529 and JP19K21317 ] and by a Health and Labour Sciences Research Grant on Intractable Disease [grant number H29-Nanchitou (Nan)-Ippan-043 ] from the Ministry of Health, Labour, and Welfare .
PY - 2020/6/15
Y1 - 2020/6/15
N2 - 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 (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. Conclusions: Our study suggests that distinct HLA-DRB1 alleles could differentially influence brain and lesion volumes over the disease course of MS.
AB - 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 (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. Conclusions: Our study suggests that distinct HLA-DRB1 alleles could differentially influence brain and lesion volumes over the disease course of MS.
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U2 - 10.1016/j.jns.2020.116768
DO - 10.1016/j.jns.2020.116768
M3 - Article
C2 - 32247967
AN - SCOPUS:85082720420
SN - 0022-510X
VL - 413
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
M1 - 116768
ER -