Abstract
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(1). Recent studies have demonstrated the presence of active inflammation in GWI(2,3) and, in addition, a positive association of the levels of C-reactive protein (CRP), an inflammatory marker, with GWI symptom severity(3). Moreover, we have shown that GWI serum contains substances that are harmful to neural cultures(4)`, a detrimental effect that can be prevented by serum of healthy GW veterans(4) and partially so by pooled human immunoglobulin G (IgG)(5). Although possible exposure to environmental toxins in war theater has been traditionally blamed for GWI(6), the evidence above(3-5) and the fact that the disease also afflicted nondeployed veterans(7), point to other causes, including the vaccines administered to GW veterans(4,5,7), 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 previously(4). 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(8). 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.