Tsilibary Effie-Photini C, Souto Eric P, Kratzke Marian, James Lisa M, Engdahl Brian E, Georgopoulos Apostolos P
Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, Minnesota, USA.
Department of Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
J Neurol Neuromedicine. 2019 Nov 25;4(6):1-9. doi: 10.29245/2572.942x/2019/6.1255.
Gulf War Illness (GWI) is a multisystem disorder of unknown etiology that has afflicted many veterans of the 1990-91 Gulf War who have sustained progressively worsening health since the war. Recent studies have demonstrated the presence of active inflammation in GWI and, in addition, a positive association of the levels of C-reactive protein (CRP), an inflammatory marker, with GWI symptom severity. Moreover, we have shown that GWI serum contains substances that are harmful to neural cultures`, a detrimental effect that can be prevented by serum of healthy GW veterans and partially so by pooled human immunoglobulin G (IgG). Although possible exposure to environmental toxins in war theater has been traditionally blamed for GWI, the evidence above and the fact that the disease also afflicted nondeployed veterans, point to other causes, including the vaccines administered to GW veterans, such as the vaccine against anthrax. Here we present, for the first time, evidence indicating the presence of the harmful anthrax protective antigen PA63 in the serum of 15 veterans suffering from GWI, as follows. First, we confirmed that the addition of GWI serum to the culture had a detrimental effect, including decreased cell spreading and increased cell apoptosis, as reported previously. And second, we found that the concomitant addition of specific polyclonal or monoclonal antibodies against PA63 had a remarkable protective effect on N2A cultures, significantly ameliorating cell spreading and reducing cell apoptosis. These results document that the adverse effects of GWI serum on neural cultures are due, in part, to persistent pathogens derived from the anthrax vaccine. We hypothesize that these anthrax pathogens persisted in the blood of the GWI veterans tested because of inability of those veterans to make antibodies against them, probably due to lack of Human Leukocyte Antigen (HLA) protection. Finally, our findings point to a possible successful intervention in GWI consisting in neutralizing (by administering specific antibodies) and/or removing (by plasmapheresis) those harmful anthrax antigens.
海湾战争综合征（GWI）是一种病因不明的多系统疾病，折磨着许多参加过1990 - 1991年海湾战争的退伍军人，自战争以来他们的健康状况逐渐恶化。最近的研究表明，GWI存在活动性炎症，此外，炎症标志物C反应蛋白（CRP）水平与GWI症状严重程度呈正相关。此外，我们已经表明，GWI血清中含有对神经培养物有害的物质，这种有害作用可被健康的海湾战争退伍军人血清预防，部分可被人免疫球蛋白G（IgG）混合物预防。尽管传统上认为在战区可能接触环境毒素是GWI的病因，但上述证据以及该疾病也折磨未部署退伍军人这一事实，指向了其他原因，包括给海湾战争退伍军人接种的疫苗，如炭疽疫苗。在此，我们首次提供证据表明，15名患有GWI的退伍军人血清中存在有害的炭疽保护性抗原PA63，如下所示。首先，我们证实，如先前报道的那样，向培养物中添加GWI血清具有有害作用，包括细胞铺展减少和细胞凋亡增加。其次，我们发现，同时添加针对PA63的特异性多克隆或单克隆抗体对N2A培养物具有显著的保护作用，显著改善细胞铺展并减少细胞凋亡。这些结果证明，GWI血清对神经培养物的不利影响部分归因于源自炭疽疫苗的持续性病原体。我们推测，这些炭疽病原体在接受测试的GWI退伍军人血液中持续存在，是因为这些退伍军人无法产生针对它们的抗体，可能是由于缺乏人类白细胞抗原（HLA）保护。最后，我们的研究结果指出了一种可能成功干预GWI的方法，即通过（施用特异性抗体）中和和/或（通过血浆置换）去除那些有害的炭疽抗原。
