Anthrax and Gulf War Illness (GWI): Evidence for the Presence of Harmful Anthrax Antigen PA63 In the Serum of Veterans with GWI
Effie-Photini C. Tsilibary1,2, Eric P. Souto1, Marian Kratzke1,2, Lisa M. James1,2,3, Brian E. Engdahl1,2,4, Apostolos P. Georgopoulos1,2,3,5*
1Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, Minnesota, USA
2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota, USA
3Department of Psychiatry, University of Minnesota Medical School, Minneapolis, Minnesota, USA
4Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA
5Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
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 war1. Recent studies have demonstrated the presence of active inflammation in GWI2,3 and, in addition, a positive association of the levels of C-reactive protein (CRP), an inflammatory marker, with GWI symptom severity3. Moreover, we have shown that GWI serum contains substances that are harmful to neural cultures4`, a detrimental effect that can be prevented by serum of healthy GW veterans4 and partially so by pooled human immunoglobulin G (IgG)5. Although possible exposure to environmental toxins in war theater has been traditionally blamed for GWI6, the evidence above3-5 and the fact that the disease also afflicted nondeployed veterans7, point to other causes, including the vaccines administered to GW veterans4,5,7, 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 previously4. 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) protection8. 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.
DOI: 10.29245/2572.942X/2019/6.1255 View / Download Pdf