IgG Neutralizes Adverse Effects of Gulf War Illness (GWI) Serum in Neural Cultures: Paving the Way to Immunotherapy for GWI (Effie-Photini, 2018)

[adambeyoncelowe]

Gulf War Illness (GWI) is a chronic debilitating disease of unknown etiology that affects the brain and has afflicted many veterans of the 1990-91 Gulf War (GW).

We showed recently that blood serum from patients suffering from GWI exerts detrimental effects on neural cultures, including reduced growth, increased apoptosis, and disruption of neural network function.

Remarkably, these adverse effects were prevented by the concomitant addition to the culture of serum from healthy Gulf War (GW) era veterans.

We interpreted those findings1 in the context of our hypothesis that GWI is, at least partly, due to circulating pathogenic persistent antigens, probably coming from vaccines administered to GW veterans who lacked crucial Human Leukocyte Antigen (HLA) class 2 alleles3 and, therefore, could not make antibodies against those antigens; by contrast, healthy GW veterans who received the same vaccines and possessed HLA protection3 made antibodies that neutralized the various antigens.

Thus, we hypothesized that the beneficial effect of the healthy serum on preventing the adverse GWI serum effects was due to the presence of antibodies against the persistent antigens.

Here we tested this hypothesis by assessing the effect of pooled human immunoglobulin G (IgG) on ameliorating the GWI adverse effects on neural growth and apoptosis in neuroblastoma N2A cultures.

We tested this effect in 14 GWI patients and found that IgG exerted a potent ameliorating effect by inhibiting the reduction in growth and increased apoptosis of GWI serum.

These results lend support to our persistent antigen hypothesis and suggest an immunotherapy approach for treating GWI.

This approach is further strengthened by our finding that the severity of GWI neurocognitive/mood (NCM) symptoms was positively correlated with the degree of apoptosis caused by GWI serum on the neural culture, thus validating the relevance of the apoptotic effect to NCM symptomatology.

Finally, we used this relation to predict NCM scores based on the reduced apoptosis effected by IgG addition and found a predicted reduction in NCM symptom severity by ~60%.

Altogether, these findings point to the possible beneficial use of IgG in treating GWI.

Something in the serum again...

Link: http://www.jneurology.com/articles/...ural-cultures-paving-the-way-to-immunoth.html

 

[DokaGirl]

IgG was tried a number of years ago in studies with pwME. I don't recall it having much success - if it did, we should all have received it long before now.

What, if anything might this Gulf War Illness study mean for pwME?

Some in our community have traveled a lot, and have needed extra vaccinations to do so. Might the thinking in this study, re lack of Human Leukocyte Antigens apply to some pwME?

I hope they have significant success with this.

 

[DokaGirl]

Further to above, I read one of Cort Johnson's articles on IVIG:

https://www.healthrising.org/blog/2018/09/13/ivig-chronic-fatigue-syndrome-pots-fibromyalgia/

My overall take away from this article is that IgG in its various forms has been tried with mixed success in small studies, and has been around for treatment for "cfs'' since the 1990s.

ME experts, Dr. Nancy Klimas included, use this treatment.

It's very expensive - up to $100K/year, and difficult to get insurance coverage for.

Larger studies are on the horizon, and it may help in subclasses of ME.

 

[Hutan]

The sample size is frustratingly small - only 14 Gulf War Illness participants and only one control (a healthy Gulf War veteran). The reported results are very clear though, in this small sample.

Watch out for the use of Standard Error of the Mean to indicate variance (rather than standard deviation).

The authors are suggesting that specific HLA alleles are protective:

GWI participants had neurocognitive/mood symptoms and lacked any of the six HLA alleles protective for GWI (DRB1*01:01, DRB1*08:11, DRB1*13:02, DQB1*02:02, DPB1*01:01, DRB1*06:01)3. The control participant was homozygote for the DRB1*01:01 protective allele.

We interpreted those findings1 in the context of our hypothesis that GWI is, at least partly, due to circulating pathogenic persistent antigens

The study is in vitro of course. Maybe it won't be easy to get the needed antibodies through the blood-brain barrier to cells affected by the antigens causing the problem? I'm not sure how the proposed mechanism might work - whether antigens would 1. attach to or inside a (long-lived) cell permanently or 2. attach and cause a lasting or temporary problem in the cell before detaching and going on to cause a problem in another cell? (Musing way outside my knowledge).

I look forward to seeing the study replicated with a bigger sample of GWI and healthy participants. It seems important.

 

[Subtropical Island]

Personal note:
Would prefer it if studies didn’t have to try so hard to make headlines and could name the paper more realistically:
IgG *might mitigate* Adverse Effects of Gulf War Illness (GWI) Serum in Neural Cultures: *Possible lead for* Immunotherapy for GWI (Effie-Photini, 2018)

ETA I mean: These things are already exciting but why not make it clear the difference between a promising lead and an actual study with significant numbers tested.

 

[Jonathan Edwards]

I look forward to seeing the study replicated with a bigger sample of GWI and healthy participants. It seems important.

It would be if it were credible. The problem for me is that if I try to work out what explanation they are trying to build it falls apart so soon in so many places that I give up. There might of course be something here but I cannot work up enthusiasm for thinking further.

They are suggesting that there are circulating pathogenic antigens in GWI patients. What they mean is small viruses (or conceivably prions) that can produce persistent infection. They would have to be small enough to get through filters and not be detected in the serum. Something like HIV or Hep B - but unknown.

This would have to be some very specific and unusual new unknown virus. The similarity to XMRV and the stories around that is too close for comfort. This new unknown virus would have to be a contaminant in all batches of vaccine used in troops sent to the Gulf but in none of the batches of vaccine used by holidaymakers or others. I think the authors may want to get around this problem by suggesting 'multiple hit' in war veterans but viruses do not do multiple hit as a rule. The story becomes more and more atypical of anything we know at every turn.

I am also worried by the proposal that adding IgG would help if it was a virus. IgG clears viruses if working in a live person by using complement fixation or macrophage activation and phagocytosis but these mechanisms by and large do not operate in cell cultures.

I could go on for hours like this.

The great difficulty now is that there are 'peer reviewed journals' happy to publish science that makes no sense at all. So there are people in labs who know no better who run out science that makes no sense at all.