人类白细胞抗原 (HLA) 与海湾战争综合征 (GWI)：HLA-DRB1*13:02 可避免海湾战争退伍军人的皮质下萎缩。
Human Leukocyte Antigen (HLA) and Gulf War Illness (GWI): HLA-DRB1*13:02 Spares Subcortical Atrophy in Gulf War Veterans.
机构信息
Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 5541, USA; Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 5541, USA; Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
出版信息
EBioMedicine. 2017 Dec;26:126-131. doi: 10.1016/j.ebiom.2017.11.005. Epub 2017 Nov 9.
BACKGROUND
Gulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990-91 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. We reported previously on the protective role of six Human Leukocyte Antigen (HLA) alleles in GWI (Georgopoulos et al., 2016) and their association with regional brain function (James et al., 2016). More recently, we reported on the presence of subcortical brain atrophy in GWI (Christova et al., 2017) and discussed its possible relation to immune mechanisms. Here we focused on one of the six HLA GWI-protective HLA alleles, DRB1*13:02, which has been found to have a protective role in a broad range of autoimmune diseases (Furukawa et al., 2017), and tested its effects on brain volumes.
METHODS
Seventy-six Gulf War veterans (55 with GWI and 21 healthy controls) underwent a structural Magnetic Resonance Imaging (sMRI) scan to measure the volumes of 9 subcortical brain regions to assess differences between participants with (N=11) and without (N=65) HLA class II allele DRB1*13:02.
FINDINGS
We found that DRB113:02 spared subcortical brain atrophy in Gulf War veterans; overall subcortical volume was 6.6% higher in carriers of DRB113:02 (P=0.007). The strongest effect was observed in the volume of cerebellar gray matter which was 9.6% higher (P=0.007) in carriers of DRB113:02 than in non-carriers. By contrast, DRB113:01 had no effect.
INTERPRETATION
These findings document the protective effect of DRB113:02 on brain atrophy in Gulf War veterans and are in keeping with recent results documenting sharing of brain mechanisms between GWI and other immune-related diseases (Georgopoulos et al., 2017). We hypothesize that the protective role of DRB113:02 is due to its successful elimination of external antigens to which Gulf War veterans were exposed, antigens that otherwise would persist causing low-grade inflammation and possibly leading to autoimmunity.
FUNDING SOURCE
U.S. Department of Defense (W81XWH-15-1-0520), Department of Veterans Affairs, American Legion Brain Sciences Chair, and University of Minnesota.
背景
海湾战争病（Gulf War Illness，GWI）是一种多系统疾病，影响了大量在 20 世纪 90 年代至 21 世纪初海湾战争中服役的退伍军人。大脑明显受到影响，表现为存在神经、认知和情绪症状。我们之前报道了六种人类白细胞抗原（Human Leukocyte Antigen，HLA）等位基因在 GWI 中的保护作用（Georgopoulos 等人，2016 年）及其与区域大脑功能的关联（James 等人，2016 年）。最近，我们报道了 GWI 中存在皮质下脑萎缩（Christova 等人，2017 年），并讨论了其与免疫机制的可能关系。在这里，我们专注于六种 GWI 保护性 HLA 等位基因之一的 DRB1*13:02，该基因在广泛的自身免疫性疾病中被发现具有保护作用（Furukawa 等人，2017 年），并测试了它对大脑体积的影响。
方法
76 名海湾战争退伍军人（55 名患有 GWI，21 名健康对照）接受了结构磁共振成像（sMRI）扫描，以测量 9 个皮质下脑区的体积，以评估 HLA 类 II 等位基因 DRB1*13:02 存在（N=11）和不存在（N=65）的参与者之间的差异。
结果
我们发现，DRB113:02 可避免海湾战争退伍军人皮质下脑萎缩；携带 DRB113:02 的退伍军人皮质下总体积高 6.6%（P=0.007）。在携带 DRB113:02 的退伍军人中，小脑灰质体积增加了 9.6%（P=0.007），这一效应最为显著，而在非携带者中则没有这种效应。相比之下，DRB113:01 没有影响。
解释
这些发现记录了 DRB113:02 对海湾战争退伍军人脑萎缩的保护作用，与最近记录 GWI 与其他免疫相关疾病之间存在共同脑机制的结果一致（Georgopoulos 等人，2017 年）。我们假设，DRB113:02 的保护作用是由于其成功消除了海湾战争退伍军人接触到的外部抗原，这些抗原否则会持续存在，导致低度炎症，并可能导致自身免疫。
资金来源
美国国防部（W81XWH-15-1-0520）、美国退伍军人事务部、美国军团脑科学主席和明尼苏达大学。
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