Risk HLA-DRB1 alleles differentially influence brain and lesion volumes in Japanese patients with multiple sclerosis
Risk HLA-DRB1 alleles differentially influence brain and lesion volumes in Japanese patients with multiple sclerosis
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风险 HLA-DRB1 等位基因对日本多发性硬化症患者的大脑和病变体积有不同影响
DOI：
10.1016/j.jns.2020.116768
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发表时间：
2020
影响因子：
4.4
通讯作者：
Kira J.
中科院分区：
文献类型：
--
作者：
Fukumoto S;Nakamura Y;Watanabe M;Isobe N;Matsushita T;Sakoda A;Hiwatashi A;Shinoda K;Yamasaki R;Tsujino A;Kira J.
背景：不同的人类白细胞抗原等位基因对大脑和病变体积的影响仍有待确定，特别是在非高加索人群中。两个不同的易感等位基因DRB1*15：01和DRB1*04：05在日本人群中流行；方法：对66例多发性硬化(MS)患者(复发缓解期50例，进展期16例)进行头颅MRI容积测量，测量液体衰减反转恢复(FLAIR)和T1病变体积，并测量标准化的全脑(NWBV)、白质(NWMV)、灰质(NGMV)、皮质灰质(NCGMV)、深部灰质(NDGMV)和丘脑(NTV)体积。结果：HLADRB1*15：01(+)*04：05(−)和HLADRB1*15：01(−)*04：05(+)携带者分别占25.8%和31.8%。HLA-DRB1*15：01携带者的病程与NWBV呈负相关(rS=−0.484，p=。036)，NWMV(Rs=−0.593，p=.和nTV(rS=−0.572，p=.病程与FLAIR呈正相关(rS=0.539，p=.和T1病变体积(rS=0.545，p=.016)。相比之下，在HLA-DRB1*04：05携带者中，未发现任何MRI参数与病程显著相关。HLADRB1*15：01携带者的NWBV和NWMV病程下降速度明显快于DRB1*15：01非携带者，NDGMV小于DRB1*15：01非携带者；而HLADRB1*04：05携带者的FLAIR和T1病变体积增加速度明显慢于非DRB1*04：05携带者。结论：我们的研究表明，不同的HLA-DRB1等位基因可能在MS的病程中不同地影响脑和病变体积。
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% and31.8% 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.