风险HLA - DRB1等位基因对日本多发性硬化症患者的脑容量和病灶体积有不同影响。

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

作者信息

Fukumoto Shoko, Nakamura Yuri, Watanabe Mitsuru, Isobe Noriko, Matsushita Takuya, Sakoda Ayako, Hiwatashi Akio, Shinoda Koji, Yamasaki Ryo, Tsujino Akira, Kira Jun-Ichi

机构信息

Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Neurology, Fukuoka Central Hospital, International University of Health and Welfare, Fukuoka, Japan.

出版信息

J Neurol Sci. 2020 Jun 15;413:116768. doi: 10.1016/j.jns.2020.116768. Epub 2020 Mar 4.

DOI:10.1016/j.jns.2020.116768

PMID:32247967

Abstract

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, DRB115:01 and DRB104:05, 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-DRB115:01(+)04:05(-) and HLA-DRB115:01(-)04:05(+) comprised 25.8% and 31.8% of patients, respectively. HLA-DRB115:01 carriers showed negative correlations between disease duration and NWBV (r = -0.484, p = .036), NWMV (r = -0.593, p = .008), and NTV (r = -0.572, p = .011), and positive correlations between disease duration and FLAIR (r = 0.539, p = .017) and T1 lesion volumes (r = 0.545, p = .016). By contrast, no significant correlation of any MRI parameters with disease duration was found in HLA-DRB104:05 carriers. HLA-DRB115:01 carriers had a significantly faster reduction in NWBV and NWMV by disease duration and smaller NDGMV than DRB115:01 non-carriers, whereas HLA-DRB104:05 carriers had a significantly slower increase in FLAIR and T1 lesion volumes than HLA-DRB104:05 non-carriers.

CONCLUSIONS

Our study suggests that distinct HLA-DRB1 alleles could differentially influence brain and lesion volumes over the disease course of MS.

摘要

背景

不同的人类白细胞抗原（HLA）等位基因对脑容量和病灶体积的影响尚待确定，尤其是在非白种人群体中。两种不同的易感等位基因，DRB115:01和DRB104:05，在日本人群中普遍存在；因此，我们旨在阐明HLA-DRB1等位基因对多发性硬化症（MS）患者脑容量和病灶体积的影响。

方法

共有66例MS患者（50例复发缓解型，16例进展型）接受了脑部磁共振成像（MRI）容积测定，测量了液体衰减反转恢复（FLAIR）和T1加权像上的病灶体积，以及标准化全脑（NWBV）、白质（NWMV）、灰质（NGMV）、皮质灰质（NCGMV）、深部灰质（NDGMV）和丘脑（NTV）体积，并进行了HLA-DRB1基因分型。

结果

HLA-DRB115:01(+)04:05(-)和HLA-DRB115:01(-)04:05(+)携带者分别占患者的25.8%和31.8%。HLA-DRB115:01携带者的病程与NWBV（r = -0.484，p = 0.036）、NWMV（r = -0.593，p = 0.008）和NTV（r = -0.572，p = 0.011）呈负相关，与FLAIR（r = 0.539，p = 0.017）和T1加权像上的病灶体积（r = 0.545，p = 0.016）呈正相关。相比之下，在HLA-DRB104:05携带者中，未发现任何MRI参数与病程有显著相关性。与DRB115:01非携带者相比，HLA-DRB115:01携带者的NWBV和NWMV随病程的减少明显更快，NDGMV更小；而HLA-DRB104:05携带者的FLAIR和T1加权像上的病灶体积增加明显比HLA-DRB104:05非携带者慢。