Chronic helminth infections induce immunomodulation:

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Chronic helminth infections induce immunomodulation:

Postby Lyon » Thu Jun 07, 2007 3:22 pm

By now everyone is probably aware of my long fascination and obsession with the (strong) possibility that the loss of "evolutionary normal" conditions (Hygiene Hypothesis) in the "developed" populations led to those same populations having a primary predisposition to allergy, asthma and autoimmune disease.

Although most of her early work was specific to allergies and asthma, Maria Yazdanbakhsh of Leiden University is an eminent pioneer in this infant field of research.
Bob


Immunobiology. 2007;212(6):475-90. Epub 2007 Apr 20.
Chronic helminth infections induce immunomodulation: Consequences and mechanisms.
van Riet E, Hartgers FC, Yazdanbakhsh M.

Department of Parasitology, Leiden University Medical Centre, Leiden, The Netherlands.

Worldwide, more than a billion people are infected with helminths. These worm infections generally do not lead to mortality, however, they are chronic in nature and can lead to considerable morbidity. Immunologically these infections are interesting; chronic helminth infections are characterized by skewing towards a T helper 2 type response as well as regulatory responses. The regulatory network is associated with chronic helminth infections and is thought to prevent strong immune responses against parasitic worms, allowing their long-term survival and restricting pathology. This regulatory network is thought to also temper responses to non-helminth antigens, like allergens or self-antigens, possibly leading to lower prevalence of allergies and autoimmune diseases in subjects that are chronically infected with helminths. This raises the interesting idea that helminths may bear molecules that have potential therapeutic action against allergies and possibly other inflammatory diseases. However, on the other side of the coin, this would predict that helminth infected subjects might not respond strongly to third party antigens like vaccines. This is an important issue, since most vaccines that are being developed against diseases such as HIV, tuberculosis or malaria will be introduced in areas where helminth infections are highly prevalent. Moreover, these vaccines are proving difficult to develop and are often weak, thus any confounder that would affect their efficacy needs to be taken into consideration. Helminth derived molecules have been identified that induce T helper 2 and regulatory responses via modulation of dendritic cells and some appear to do so via Toll like receptor (TLR) signaling. New insights into these pathways could be useful to antagonize suppression and hence boost vaccine efficacy or to optimize suppression induced by helminth derived molecules and control inflammatory diseases.

PMID: 17544832 [PubMed - in process]
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Postby hummingbird68 » Thu Jun 21, 2007 8:06 pm

Where can I get some worms??? I would seriously eat some to help my MS and asthma.

I have been following the studies showing that Crohn's and MS symptoms are helped by parasite infestations.

No seriously, I have been fascinated by the hygiene hypothesis since I heard of it in pharmacy school. It really applies to me. I'm the oldest child, my mom was a clean freak, then I developed severe asthma/allergies and the doctor said to keep me away from other sick people so I wouldn't end up in the hospital with an asthma attack. I have always had problems with viruses. I had EBV in 1985 and my first case of ON in 1990. I was recently diagnosed with MS even though I have had symptoms since 1999. My MS specialist's eyes lit up when I told him I had a severe case of mono...he said I think you have MS even before seeing my MRI. (He is the MS guru!)

Anyways, I do eat sushi ... I can always hope! AND I did live in a 3rd world country for 3 years.

Are there any studies on this subject being conducted in this country???

Rachel (pharmacist)
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Postby hummingbird68 » Thu Jun 21, 2007 8:08 pm

How is the Tovaxin trial going for your wife??? I originally wanted to be in the study but was talked out of it by family. I'm in a different study now. Tovaxin sounds very promising, I invested in Opexa.

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Postby Wonderfulworld » Fri Jun 22, 2007 3:26 am

Thanks for that interesting article Bob.

And Rachel, reading your post is very like reading about my own history, I am a first child too, obsessively clean parents, got asthma and allergies, parents avoided people and situations that were very 'germy' (disinfectant-wiped public phones before use- how embarrasing as a child!).

Got Mono aged 19, then dx'ed MS by age 26, 9 years ago.

Making an admission here, I, and most of my classmates, got worms when we were about 8 years old 8O Yuk. My parents dosed me a few times to get rid of them, they were very unpleasant! But I think the helminths in the study are a different type....

Worms or injections....an interesting choice, but I'd go with worms if I could get the right ones too :)
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Postby Lyon » Fri Jun 22, 2007 6:35 am

hummingbird68 wrote:How is the Tovaxin trial going for your wife??? I originally wanted to be in the study but was talked out of it by family. I'm in a different study now. Tovaxin sounds very promising, I invested in Opexa.
Hi Rachel,
Smart move investing in Opexa! I wish I could afford to :(

My wife is doing very well, thanks. Because she's been doing so well and because this trial involves a placebo element I've been very, very hesitant to allow myself to believe it's the Tovaxin but in the last couple of days I realized that I don't think it's possible for her to have the placebo effect.

Of course the diagnosis of MS is terrifying and ANYONE would want to go back to a normal life and not have MS hanging over their head. In the past I've considered my wife's awareness of my long obsession with the autoimmunes and that maybe my confidence in Tovaxin in itself was enough to incite the placebo effect in her. Who knows, maybe that really is the case, but in reality she knows NOTHING about MS and knows nothing specific about Tovaxin and because she hasn't had further attacks, she's had the luxury of MS becoming a non issue for her.

Placebo effect requires a strong desire to surmount the illness and a strong desire for the treatment to work and she has no interest or knowledge in any of it which makes me think that she couldn't muster up a placebo effect if she wanted to so, at least to my way of thinking, she's on the real thing and went from a 3.5 EDSS to a 1.0 before the second injection and evidently is continuing to improve in other ways.

Bob
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Postby TwistedHelix » Fri Jun 22, 2007 7:16 am

Hello Bob,
As you know, I've always been very convinced by the evidence you've provided, and that our unnaturally clean and synthetic lifestyles have had a profound effect on our immune systems.
I would just take issue with your definition of the placebo effect: I don't think it's the desire for an outcome which produces that outcome, I think it's the profound belief in the treatment which can have such a powerful influence. Whether your wife has knowledge about MS and medication or not doesn't necessarily affect her belief either way, but whatever the reason, I'm really glad she's doing so well.

If it turns out that it IS your influence which has kept her well, please would you send me a tape of your soothing, guru-like meditations and sage advice?
Dom
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Postby Lyon » Fri Jun 22, 2007 9:06 am

TwistedHelix wrote: If it turns out that it IS your influence which has kept her well, please would you send me a tape of your soothing, guru-like meditations and sage advice?
:lol: :lol: Gosh! I might have found my source of income so that I can buy Opexa stock after all!!

Well before my wife was diagnosed with MS, my addiction the the autoimmune diseases and the internet were long a sore spot for her. I did and do spend every waking hour reading about autoimmune diseases, thinking about them, talking about them. After she was diagnosed, what she had earlier considered a liability became an asset.

By the way Dom, if the CD I send has you tap dancing tomorrow you are going to owe me some money. I've heard that you weren't able to tap dance even before MS!

Bob
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Postby Lyon » Fri Jun 22, 2007 3:18 pm

hummingbird68 wrote:No seriously, I have been fascinated by the hygiene hypothesis since I heard of it in pharmacy school. It really applies to me. I'm the oldest child, my mom was a clean freak, then I developed severe asthma/allergies and the doctor said to keep me away from other sick people so I wouldn't end up in the hospital with an asthma attack.

Hi Rachel,
Yes, you seriously could be the poster child for the hygiene hypothesis. Sadly, all of us in the "developed" countries are. It's just more obvious in some than others.

I wish that my mind was orderly enough that I could write a nice step by step webpage about it but I'm so obsessed with it and it's so complicated that I've tried many, many times and I end up with jumbled, unintelligible messes.

I see that you and Wonderfulworld share comparable histories. WW mentions
Wonderfulworld wrote:Making an admission here, I, and most of my classmates, got worms when we were about 8 years old Shocked Yuk. My parents dosed me a few times to get rid of them, they were very unpleasant! But I think the helminths in the study are a different type....
I contacted Dr Kurtzke several months ago to see if it was anything he'd ever heard of or considered (hygiene hypothesis/loss of evolutionary normal conditions) because I thought it would be wonderful if the guy who spent all that time collecting, compiling and analyzing MS data to try to determine the cause of MS were able to play a part in finally identifying the cause. AND to convince him that all his research and arguments which led him to the conclusion that the British soldiers MUST have spread some unidentifiable virus amongst the Faroese was imminently sensible.....EXCEPT for the fact that there likely was no virus and that the British occupation causing the loss of something which had always been present in the Faroes (parasite infestation) would paint exactly the same picture as the introduction of an unidentifiable virus.

Dr Kurtzke gets right to the point and he knows the right questions. I've given him some good answers but corresponding with him has given me good insight into the questions I need to answer to myself. Only certain helminths? Which helminths? Which are the helminths that have evolved to to survive comfortably in the human? Which are the human zoonotics (parasites adapted to other animals which can survive and modulate the human immune system but can't complete their life cycle). Considering that there are many human parasites, is it only helminth parasites which interact with the human immune system and why?

There is no doubt from Dr Kurtzke's demeanor that he wouldn't hesitate to tell me to get lost and in fact his first response was something to the effect of...I get at least one nut a month proposing the cause of MS and this isn't the first time the subject of parasites has come up. He admittedly scared me off for a month or so but I'm so convinced and there is so much evidence that I eventually wrote back.

Because it doesn't seem that he would hesitate to tell me to get lost, I think he's being honest when he says that he's very busy at the moment (working on three papers, two grants and just submitted two articles for publication) but that he will investigate and give it serious consideration when his schedule eases. That's fine with me because it buys me a bit of time to try to determine more answers.

I think anyone's initial consideration should be that the purpose of your immune system is to kill or expel anything that isn't "you", so anything able to survive your immune system should be suspect. Whether helminth, virus, bacteria or protozoan, how is it able to survive the immune system because there is no doubt that it is doing SOMETHING to keep the immune system off it's back.

Originally I assumed that because viruses and bacteria hide in our cells, hiding was their only needed evasion method. But they are exposed when multiplying and I've read research documenting bacteria having specific immune modulating effects.

To emphasize how diverse and complicated the situation can be, read this abstract from the April 2007 Journal of Neuroimmunology http://tinyurl.com/38sq36 Basically, to rid themselves of malaria, Sardinia Italy eliminated the mosquitos which carry the parasite which causes malaria. Now Sardinia is experiencing high rates of MS. I read the entire article about three times and I can't figure out what they're trying to prove regarding genetics but the point is that even ridding themselves of the parasite which causes malaria increased the MS incidence.

On the other hand here is an abstract regarding H pylori bacteria providing protection from MS http://tinyurl.com/2wfpgg .......with it in mind that even though H pylori is an intestinal parasite responsible for peptic ulcers and the digestive tract is considered "external", when the H pylori interacts with blood it can have an internal interaction with the immune system.

You've both experienced mono (or at least exposure to EBV), depite the fact that it may seem that way, in this situation I don't think it's contrary to consider that a virus may be protective and at the same time a possible instigator in the autoimmune process itself.

Considering the amount of infestation humans have historically experienced, one short exposure to worms wasn't likely nearly enough to offer more than temporary benefit.

Rachel, you said you were interested in the hygiene hypothesis. Doesn't it seem a little eerie that when David P. Strachan postulated it in 1989 that he was only considering allergies, in fact at that time allergies and autoimmune diseases were considered almost opposites, driven by "opposing" TH responses. Yet the evidence showed him that exposure to "evolutionary normal" conditions led to a "mature" immune system, which by the age of 14 or 15 was able to provide protection through life.

On the other hand, completely independently, using incidence data (I think Dr Kurtzke did it) MS researchers found that someone migrating from a country of low MS incidence AFTER about the age of 14 or 15 keeps the lower incidence level of the country the migrated from...for life.

Just one more of about a zillion, admittedly circumstantial, evidences pointing to the loss of evolutionary normal conditions leading to MS/autoimmune diseases, allergy, asthma.

hummingbird68 wrote:Are there any studies on this subject being conducted in this country???
Lots of research in the US and all over the world but the only study specific to MS is that John Fleming at the University of Wisconsin has a $358,000 grant from the NMSS http://tinyurl.com/3e3vcb to do a T suis/MS clinical trial but the FDA hasn't cleared the way yet.

Bob
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