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Severe Food Allergies Turned Off in Mice

guest

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There is still a long way to go before we can prevent allergic reactions but this should be a first step. Unfortunately most PWCs suffer from food intolerances which are different from allergies so the relevance of this study is lowered but it's interesting anyways.

http://www.sciencedaily.com/releases/2010/10/101001163344.htm

ScienceDaily (Oct. 2, 2010) — Johns Hopkins scientists have discovered a way to turn off the immune system's allergic reaction to certain food proteins in mice, a discovery that could have implications for the millions of people who suffer severe reactions to foods, such as peanuts and milk.
The findings, published online in the journal Nature Medicine, provide hope that the body could [under close medical supervision] be trained to tolerate food allergies that lead to roughly 300,000 emergency room visits and 100 to 200 deaths each year.
The research team, led by Shau-Ku Huang, Ph.D., a professor of medicine, and Yufeng Zhou, M.D., Ph.D., a postdoctoral fellow in the Division of Allergy and Clinical Immunology at Johns Hopkins University School of Medicine, discovered that one kind of immune cell in the gastrointestinal tract called lamina propria dendritic cells (LPDC) -- considered the first line of defense for a body's immune system -- expresses a special receptor, SIGNR1, which appears on the cells' surface and binds to specific sugars.
By targeting this receptor using sugar-modified protein, researchers were able to keep food proteins that would have induced a severe, even deadly, allergic reaction from causing any serious harm.
"There is no cure for food allergies, and the primary treatment is avoidance of the offending protein," Zhou says. "This could teach our bodies to create a new immune response and we would no longer be allergic to the protein."
The researchers hope to confirm whether this promising process in mice can also occur in people.
Food allergies are triggered by the immune system and, in some people, can cause severe symptoms or even a life-threatening reaction known as anaphylaxis. In the United States, it is estimated that six to eight percent of children under the age of three and nearly four percent of adults have food allergies, and the prevalence is rising. Because of the extreme difficulty in avoiding all food allergen exposure and the lack of effective treatments, preventive and therapeutic strategies are urgently needed, Zhou says.
In the laboratory, Zhou and his colleagues took a food protein that causes allergies in mice and modified it by adding special sugars. They hypothesized that, when ingested by the mice, the modified proteins would be able to bind to what are known as the SIGNR1 receptors on the immune system cells. Bound in this way, the immune system would learn to tolerate the modified food protein -- and the protein would no longer induce an allergic reaction, even when consumed in its unmodified form.
Zhou fed his mice the modified protein once a day for three days. Five days later, he tested them by feeding them the protein in its unmodified form. Another group of mice was not fed the modified protein at all. The severity of the allergic response to the unmodified protein -- which in the control-group mice tended to be tremors, convulsions and/or death -- was significantly decreased in those mice that had been pre-fed the modified protein. Some still had minor reactions like itchiness or puffiness around the eyes and snout, but none had serious ones. These mice appeared to be desensitized to the food protein, even when it was fed to them in its unmodified form, says Zhou. In this model, SIGNR1 plays a key role in shutting off some responses in the immune cells, but whether this is the only function of this receptor is, at present, unknown.
Other Johns Hopkins researchers on the study include Hirokazu Kawasaki, Shih-Chang Hsu, Reiko T. Lee, Xu Yao, Beverly Plunkett, Jinrong Fu and Yuan C. Lee.
Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Johns Hopkins Medical Institutions.
Journal Reference:
Yufeng Zhou, Hirokazu Kawasaki, Shih-Chang Hsu, Reiko T Lee, Xu Yao, Beverly Plunkett, Jinrong Fu, Kuender Yang, Yuan C Lee, Shau-Ku Huang. Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1. Nature Medicine, 2010; DOI: 10.1038/nm.2201
 

xchocoholic

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Zhou fed his mice the modified protein once a day for three days. Five days later, he tested them by feeding them the protein in its unmodified form. Another group of mice was not fed the modified protein at all. The severity of the allergic response to the unmodified protein -- which in the control-group mice tended to be tremors, convulsions and/or death -- was significantly decreased in those mice that had been pre-fed the modified protein. Some still had minor reactions like itchiness or puffiness around the eyes and snout, but none had serious ones. These mice appeared to be desensitized to the food protein, even when it was fed to them in its unmodified form, says Zhou. In this model, SIGNR1 plays a key role in shutting off some responses in the immune cells, but whether this is the only function of this receptor is, at present, unknown.

Thanks for posting this. I'm still too new to biochemistry to understand it but I was wondering why he waited 5 days before challenging the mice with the known food intolerance. I'm not up on mouse digestive tracts either so I'm not even sure if they have villi or zonulin or different parts to their digestive tracts like we do.

I'm not sure how this would work for those of us with multiple food intolerances caused by leaky gut. And I can't see a way this would work for chemical intolerances either.

Interesting idea of using a sugar to modify the protein though ... why not use fats ? again thanks for the article ... someday all the pieces will come together for us ... x
 

guest

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320
Thanks for posting this. I'm still too new to biochemistry to understand it but I was wondering why he waited 5 days before challenging the mice with the known food intolerance. I'm not up on mouse digestive tracts either so I'm not even sure if they have villi or zonulin or different parts to their digestive tracts like we do.

I'm not sure how this would work for those of us with multiple food intolerances caused by leaky gut. And I can't see a way this would work for chemical intolerances either.

Interesting idea of using a sugar to modify the protein though ... why not use fats ? again thanks for the article ... someday all the pieces will come together for us ... x

Ye, I hope so. Maybe he waited 5 days in order to show that the effect is not short-dated (e.g. only some hours). I also think that this has only very little implications for intestinal permeability because the allergic reaction happens very quickly while food intolerances or their symptoms can be delayed.
 

xchocoholic

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good point ... I'm not convinced though that allergies are always apparent within a short period of time. My DD has anaphylaxis from peanuts and possibly other molds but she doesn't always react right away and sometimes she doesn't react at all. This made if very difficult for me to keep her from eating Reese's peanut butter cups when she was 16 once she figured this out ... oh and FWIW ... she now gets severe digestive symptoms from peanuts. She hasn't had anaphylaxis in a long time.

See, I was thinking that when the mice were fed the proteins that they were allergic to at hours 1, 2, 3, etc and days 1, 2, 3 and 4 they didn't fare as well. Meaning, it took 5 days for the mice to recover enough from this experiment to survive eating those proteins again.

It's great that they are looking at this sort of option though. Any ideas if others have already experimented with this ? There appears to a massive overlay in medical studies ... tc ... x
 
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