Lysandropoulos Andreas P, Mavroudakis Nicolas, Pandolfo Massimo, El Hafsi Kaoutar, van Hecke Wim, Maertens Anke, Billiet Thibo, Ribbens Annemie
Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
J Neurol Sci. 2017 Apr 15;375:348-354. doi: 10.1016/j.jns.2017.02.019. Epub 2017 Feb 16.
The identification of a biomarker with prognostic value is an unmet need in multiple sclerosis (MS). The objective of this study was to investigate a possible association of HLA genotype with disease status and progression in MS, based on comprehensive and sensitive clinical and magnetic resonance imaging (MRI) parameters to measure disease effects.
A total of 118 MS patients (79 females, 39 males) underwent HLA typing. Patient MS status was assessed at two time points in a 2-year interval, based on clinical scores (including EDSS, MSSS, T25FW, 9-HPT, SDMT, BVMT, CVLT-II) and MRI evaluations. Quantitative brain MRI values were obtained for whole brain atrophy, FLAIR lesion volume change and number of new lesions using MSmetrix. Predefined HLA patient groups were compared as of disease status and progression. Global assessment was achieved by an overall t-statistic and assessment per measurement by a Welch test and/or Mann Whitney U test. The effects of multiple covariates, including age, gender and disease duration as well as scan parameters, were also evaluated using a regression analysis.
The HLA-A02 allele was associated with better outcomes in terms of MSSS, EDSS and new lesion count (Welch test p-value<0.05). The HLA-B07 and HLA-B44 alleles showed a global negative effect on disease status, although none of the measurements reached significance (p-value<0.05). Results for the HLA-DRB115, HLA-DQB106 and HLA-B08 alleles were inconclusive. The influence of the confounding variables on the statistical analysis was limited.
鉴定具有预后价值的生物标志物是多发性硬化症（MS）中尚未满足的需求。本研究的目的是基于全面且敏感的临床和磁共振成像（MRI）参数来测量疾病影响，探讨HLA基因型与MS疾病状态和进展之间的可能关联。
共有118例MS患者（79例女性，39例男性）接受了HLA分型。基于临床评分（包括扩展残疾状态量表[EDSS]、多发性硬化症综合评分量表[MSSS]、25英尺步行时间[T25FW]、9孔插板试验[9-HPT]、符号数字模式测验[SDMT]、波士顿命名测验[BVMT]、加利福尼亚语言学习测验第二版[CVLT-II]）和MRI评估，在两年间隔的两个时间点评估患者的MS状态。使用MSmetrix获取全脑萎缩、液体衰减反转恢复序列（FLAIR）病灶体积变化和新病灶数量的定量脑MRI值。比较预定义的HLA患者组的疾病状态和进展情况。通过总体t检验进行整体评估，并通过 Welch检验和/或曼-惠特尼U检验对每次测量进行评估。还使用回归分析评估了包括年龄、性别和疾病持续时间以及扫描参数在内的多个协变量的影响。
就MSSS、EDSS和新病灶计数而言，HLA-A02等位基因与更好的预后相关（Welch检验p值<0.05）。HLA-B07和HLA-B44等位基因对疾病状态显示出总体负面影响，尽管没有一项测量达到显著水平（p值<0.05）。HLA-DRB115、HLA-DQB106和HLA-B08等位基因的结果尚无定论。混杂变量对统计分析的影响有限。
