Vol 4-6 Research Article

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
Vol 5-1 Research Article

Tri-Allelic Human Leukocyte Antigen (HLA) Protection Against Dementia

Lisa M. James1,2,3, Apostolos P. Georgopoulos1,2,3,4*

1Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, USA

2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, USA

3Department of Psychiatry, University of Minnesota Medical School, Minneapolis, USA

4Center for Cognitive Sciences, University of Minnesota, Minneapolis, USA

5Department of Neurology, University of Minnesota Medical School, Minneapolis, USA

Human Leukocyte Antigen (HLA) Class II DRB1*13:02 has recently been found to protect against dementia in Continental Western Europe. Here we extend those findings by evaluating the association between the population frequency of two additional Class II HLA alleles – DRB1*01:01 and DRB1*15:01 – alone and in combination with DRB1*13:02, on dementia prevalence in Continental Western Europe. Results indicated that the prevalence of dementia in 14 Continental Western European (CWE) countries significantly decreased exponentially with increasing frequency of any of the three alleles alone and in combination (P’s < 0.001). When combined, the population frequency of the three alleles accounted for 67% of the variance in dementia prevalence. The combined frequency of DRB1*01:01, DRB1*13:02, and DRB1*15:01 was also significantly associated with dementia prevalence in those aged 65 years and older (P = 0.004) and with a change in dementia prevalence between 1990 and 2016 (P = 0.006). These findings, which document the protective effects of three common Class II HLA alleles on dementia prevalence in CWE, are discussed in terms of the role of HLA class II genes in pathogen elimination. More specifically, we hypothesize that dementia prevalence is higher for countries in which the population frequency of these protective alleles is low, prohibiting the successful elimination of pathogens that may play a causal role in dementia.

DOI: 10.29245/2572.942X/2019/1.1261 View / Download Pdf
Vol 5-1 Case Report

Acute Fatal Stroke Associated with Honeybee Sting

Ashutosh Gupta

Consultant Neurologist, Department of Neurology, Shree Aggarsain International Hospital, Rohini, Delhi, India

The venom toxins of honeybee cause anaphylactic allergic reactions and/or any type of stroke. Hemorrhagic strokes are more severe than the ischemic strokes. Diverse pathophysiological mechanisms have been postulated for occurrence of these strokes. We discuss here mechanism of acute fatal hemorrhagic and ischemic stroke in a middle age woman, stung by the honeybee on her right arm and who clinically manifested loss of consciousness and tonic clonic seizure, within 3-4 hours followed by hemiparesis. The MRI revealed brain lesions of multiple infarctions with hemorrhagic transformation, subdural (SDH) and subarachnoid (SAH) hemorrhages. This appears to be the first report, wherein a patient had entire spectrum of stroke (infarcts, subarachnoid and subdural hemorrhages), after a single inciting event of bee sting.

DOI: 10.29245/2572.942X/2019/1.1262 View / Download Pdf
Vol 5-1 Review Article

The Triple Functional Domain Protein Trio with Multiple Functions in the Nervous System

Tao Tao*, Jie Sun, Min-Sheng Zhu

Model Animal Research Center, State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing University, China

DOI: 10.29245/2572.942X/2019/1.1263 View / Download Pdf
Vol 5-1 Research Article

Dementias Caused by Persistent Pathogens and the Protective Role of HLA Against them

Lisa M. James1,2,3, Apostolos P. Georgopoulos1,2,3,4*

1Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, USA

2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, USA

3Department of Psychiatry, University of Minnesota Medical School, Minneapolis, USA

4Department of Neurology, University of Minnesota Medical School, Minneapolis, USA

Dementia is a leading cause of death worldwide, representing a significant global burden. In addition to genetic and lifestyle factors that have been widely linked to dementia, pathogens are increasingly recognized as contributing to the development of dementia. Here we discuss the role of human leukocyte antigens (HLA) in maintaining brain health by facilitating the elimination of pathogens and highlight evidence suggesting that the inability to eliminate pathogens contributes to dementia. Finally, we briefly review common forms of dementia including Alzheimer’s disease, vascular dementia, frontotemporal dementia, Lewy body dementia, and prion dementia in an effort to contextualize the role of persistent pathogens across the various dementia phenotypes.

DOI: 10.29245/2572.942X/2019/1.1260 View / Download Pdf