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对海湾战争综合症退伍军人进行新型中枢神经系统生物标志物筛查。

Screening for novel central nervous system biomarkers in veterans with Gulf War Illness.

作者信息

Abou-Donia Mohamed B, Conboy Lisa A, Kokkotou Efi, Jacobson Eric, Elmasry Eman M, Elkafrawy Passent, Neely Megan, Bass Cameron R 'Dale', Sullivan Kimberly

机构信息

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, United States.

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.

出版信息

Neurotoxicol Teratol. 2017 May;61:36-46. doi: 10.1016/j.ntt.2017.03.002. Epub 2017 Mar 9.

Abstract

Gulf War illness (GWI) is primarily diagnosed by symptom report; objective biomarkers are needed that distinguish those with GWI. Prior chemical exposures during deployment have been associated in epidemiologic studies with altered central nervous system functioning in veterans with GWI. Previous studies from our group have demonstrated the presence of autoantibodies to essential neuronal and glial proteins in patients with brain injury and autoantibodies have been identified as candidate objective markers that may distinguish GWI. Here, we screened the serum of 20 veterans with GWI and 10 non-veteran symptomatic (low back pain) controls for the presence of such autoantibodies using Western blot analysis against the following proteins: neurofilament triplet proteins (NFP), tubulin, microtubule associated tau proteins (Tau), microtubule associated protein-2 (MAP-2), myelin basic protein (MBP), myelin associated glycoprotein (MAG), glial fibrillary acidic protein (GFAP), calcium-calmodulin kinase II (CaMKII) and glial S-100B protein. Serum reactivity was measured as arbitrary chemiluminescence units. As a group, veterans with GWI had statistically significantly higher levels of autoantibody reactivity in all proteins examined except S-100B. Fold increase of the cases relative to controls in descending order were: CaMKII 9.27, GFAP 6.60, Tau 4.83, Tubulin 4.41, MAG 3.60, MBP 2.50, NFP 2.45, MAP-2 2.30, S-100B 1.03. These results confirm the continuing presence of neuronal injury/gliosis in these veterans and are in agreement with the recent reports indicating that 25years after the war, the health of veterans with GWI is not improving and may be getting worse. Such serum autoantibodies may prove useful as biomarkers of GWI, upon validation of the findings using larger cohorts.

摘要

海湾战争综合征(GWI)主要通过症状报告进行诊断;需要客观的生物标志物来区分患有GWI的人。在流行病学研究中,部署期间先前的化学暴露与患有GWI的退伍军人中枢神经系统功能改变有关。我们小组之前的研究表明,脑损伤患者存在针对必需神经元和神经胶质蛋白的自身抗体,并且自身抗体已被确定为可能区分GWI的候选客观标志物。在这里,我们使用针对以下蛋白质的蛋白质印迹分析,筛查了20名患有GWI的退伍军人和10名有症状(腰痛)的非退伍军人对照的血清中是否存在此类自身抗体:神经丝三联体蛋白(NFP)、微管蛋白、微管相关tau蛋白(Tau)、微管相关蛋白-2(MAP-2)、髓鞘碱性蛋白(MBP)、髓鞘相关糖蛋白(MAG)、胶质纤维酸性蛋白(GFAP)、钙调蛋白激酶II(CaMKII)和神经胶质S-100B蛋白。血清反应性以任意化学发光单位测量。作为一个群体,患有GWI的退伍军人在除S-100B之外的所有检测蛋白质中,自身抗体反应性水平在统计学上显著更高。病例相对于对照的增加倍数从高到低依次为:CaMKII 9.27、GFAP 6.60、Tau 4.83、微管蛋白4.41、MAG 3.60、MBP 2.50、NFP 2.45、MAP-2 2.30、S-100B 1.03。这些结果证实了这些退伍军人中持续存在神经元损伤/神经胶质增生,并且与最近的报告一致,这些报告表明战争25年后,患有GWI的退伍军人的健康状况没有改善,可能还在恶化。在使用更大的队列验证这些发现后,此类血清自身抗体可能被证明是GWI的有用生物标志物。

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