Peanut allergy cured in majority of children in immunotherapy trial
theguardian.com
theguardian.com
While both peanut allergy and celiac disease involve pathogenic immune responses, they represent very different types of problems and this study's results do not suggest any relevance to celiac.
The peanut allergies that they are referring to in this study are one of the most striking examples of what's known as a Type I hypersensitivity (IgE-mediated/anaphylaxis). In this type of reaction, high levels of IgE, a class of antibody, generated toward a specific antigen become loaded onto mast cells and on re-exposure, cause mast cell degranulation and subsequent smooth muscle contraction. For this reason, anaphylactic responses frequently involve closing of the airway, nausea/vomiting, and other dysregulations of smooth muscle activation and require a strong adrenurgic agonist like epinephrine to counteract this activation.
Celiac pathogenesis is not a Type I hypersensitivity. To my knowledge, the exact mechanism of pathogenesis is not known, but it is likely a combination of Type III (antibody-mediated) and Type IV (T-cell mediated) hypersenitivities.
Anyway, I'm not trying to ruin anyone's hope here, but this study has no relevance for celiac. What this has shown is that there is the potential for food allergies to be systematically eliminated with long-term increasing exposure to the problematic antigen, in this case, peanut antigen. This has been done for some time with other, less aggressive types of IgE-mediated conditions like dog and cat dander allergies. So in that way, it's not all that surprising of a result, but I'm certainly glad to see that this was able to be done safely. This is really great news for the millions of people out there with anaphylactic food allergies.
All that being said, I do hope that celiac can be managed more effectively with immune-modulatory (or other) treatments in the future and my sympathies go out to those who have been affected by this horrible disease.
Can you link to this please? Is this "allergen immunotherapy"[0]?
[0] https://en.m.wikipedia.org/wiki/Allergy_to_cats#Allergy_shot...
Hope that's helpful.
In regards to autoimmunity, antigens themselves don't destroy cells--antigens only provoke a pathogenic immune response when presented to the immune system.
< Celiac is typically an autoimmune response to Gliadin protein as a result of human leukocyte activation genes HLA-DQ2.2/2.5 or HLA-DQ8. In either case, it is happening at the cellular level for every cell that comes into contact with the protein.
You're not wrong with regards to the celiac, gliadin, and the association with the HLA alleles that you've mentioned. However, I'll point out that those particular HLA genes make up MHC class II proteins. These are the proteins present on what are known as professional antigen presenting cells, a small group of specialized immune cells throughout the body. MHCII proteins present foreign antigen to TH4 cells (helper T cells) which can then activate a larger immune response.
Epithelial cells of the intestinal villi have not classically been thought to be professional antigen presenting cells, and thus should have very small levels of expression. I found one older study (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC508181/) that suggests these intestinal villi cells can express class II but nothing since. All of this suggests that the pathogenesis of celiac disease is not as simple as intestinal villi cells expressing high levels of the HLA proteins encoded by the genes you mentioned and provoking a direct immune response--rather, like seemingly every autoimmune disease, the story is much more complicated and likely involves the activation of CD4+ T cells, generation of pathogenic autoantibodies, and a larger network of pro-inflammatory players.
Isn't the damage to villi a byproduct of the (auto)immune reaction? I haven't studied it in depth, but what I've read seems to indicate that the damage is caused by inflammatory reactions (as part of the immune response) rather than directly from the prolamins.
> The antigen will always destroy your cells, autoimmune response or not. Sensitivity depends on how many (one or two) of the HLA genes you have that react with gluten.
The gluten is not reacting with genes, but the genes help determine how your immune system responds to the antigen, so it's still entirely an immune response, at least as I understand it.
I have it nowhere near as bad as you (which is why it went undiagnosed until I was 30... although it's still pretty bad). But for about 5 years after I found out I would have recurring dreams where I would be eating a hamburger and realize after swallowing "Oh, crap, that's a normal bun!" I suppose in some sense that might qualify as a nightmare the first couple of times, because it would fully wake me up.
Another funny angle--I also have Type 1 diabetes (diagnosed when I was 9) and for a long time after diagnosis I had dreams about drinking a 64oz soda only to realize it wasn't diet, and panicking since I would probably be in DKA soon after!
Maybe there is some immune system disease/nightmare link that has gone undiscovered :)
Plus - as horrible as a reaction is nothing compared to an allergic/anaphylactic response from ingesting a known allergen.
http://www.immusant.com/patient-resources/clinical-trials.ph...
Hardship at restaurants is a common thing, when people are inflexible. I felt bad for her sometimes because her boyfriend would insist on going somewhere he wanted to go, even if she wasn't able to eat anything there beyond a salad. There will probably be more of an emphasis on cooking at home, but, even then, friends and roommates can be part of it if they're just willing to make a few simple tweaks. We even managed to make fried chicken that she could eat just by tracking down a gluten-free breading option.
To boot, she's got about ten years or so before she's out on her own and this becomes her sole responsibility. My experiences are about five years old at this point, and we've already come a long way since then. In 2011, the most widespread "gluten free" option was Chipotle. Now, I see a gluten free menu at pretty much every sit-down restaurant I've gone to.
It wouldn't surprise me, the human microbiome (which includes bacteria) out numbers cells in the human body something like 100:1. They call it the second brain and just reading about some of the studies should be eye opening to many. For example, some mental health issues can be treated through the stomach and alternatively certain gasterointestinal issues can be treated via the brain.
I recall one of the more interesting studies about twins in (equatorial) Africa where obviously both nature/nurture are identical but 1 twin will be malnurished while the other is not, the only measurable difference coming from the bacteria in the gut, which impacts the ability for the body to absorb nutrients.
Truely sorry about you daughter and it seems you are keenly aware of the social impact of food. However, as someone who has self imposed restrictions it may be a blessing in disguise, because there is a very good chance greater than 10% of her peers will develop non alcoholic fatty liver disease during childhood, some childhood type 2 diabetes, and yet a significantly larger number will develop all kinds of health issues (including mental health problems) not even as of yet connected with food/nutrition. Admittedly, I'll sneak in a cheat meal and can eat at restaurants but most the time, just like most the food in grocery stores, I easily avoid because I view the same as poison. And while it may sound extreme, just look around at the people in the grocery or especially restaurants and honestly come to your own conclusion about the percentage of people who just look unhealthy.
Fake news! [1]
[1] https://www.nature.com/news/scientists-bust-myth-that-our-bo...
Further, the ratio has little to do with the actual function which is the major takeaway. Nice fake account btw!
Edit: from your article, “It is good that we all now have a better estimate to quote,” says Peer Bork, a bioinformatician at the European Molecular Biology Laboratory in Heidelberg, Germany, “But I don’t think it will actually have any biological significance.”
You’re also right to hope for better treatment paths for her future. Compared to even when we grew up the cultural knowledge of celiac is so much better. And since it’s something that’s been discovered to be not nearly as rare as once thought, the research dollars have caught up. These are all signs that point to a bright future :-)
And I agree with her quality of life being affected. Hopefully, other restaurants will catch on, similar to how we label food that may contain peanuts.
[1]http://www.nejm.org/doi/full/10.1056/NEJMoa1414850#abstract
This idea of introducing the food in an ED waiting room is probably something spread on mommy forums such as BabyCenter. One mom shares it, then there is social pressure to do the same thing. A parent probably thinks "Does it make me a bad mom if I don't do it." Very unfortunate.
Thank God I didn't feed it to him.
Prior to the recent AAP recommendation (and possibly still after it) many daycares had nut-free policies as a selling point.
> This idea of introducing the food in an ED waiting room is probably something spread on mommy forums such as BabyCenter.
Introducing an allergen with ready access to medical care may be an overreaction, but is hardly problematic.
It's the delay in introduction which is problematic, and which research suggest drove the big upswing in incidence of peanut and some other allergies.
It's important to remember how vital early introduction to both beneficial and harmful environmental agents are to human development. Its easy to have the mindset that I will wait until my child is 3+ years old before I introduce anything potentially harmful with the idea being that they will be bigger and stronger. The immune system is actually quite strong and adaptable early in development which is precisely why vaccines work better at an early age
That being said the parent (esp mother) also plays a large roll in the first introduction of helpful bacteria that break down various foods. The bacteria that are transferred during a vaginal birth give the baby a leg up in establishing its early gut flora. Additionally there is a direct transfer of antibodies through the placenta and breast milk which help protect the baby. I would imagine a mother eating peanuts during both those times would help pass some of these antibodies to her offspring.
> Looks like we guessed right on this one.
You conclude that the advice is wrong because of your sample size of however many kids you have?
You didn't explicitly say "our kids" but merely "kids"; God help you if you feed nuts to other peoples' kids based off your conclusion.
Feel free to discuss your ideas/concerns with other parents and censure them like anti-vaxxers if you want. BUT if you either 1) don't ask them first and give their kids peanuts or 2) disregard their concerns and give their kids peanuts, and a kid dies because of it, you are culpable and responsible for that kid's death.
What you have instead is milk allergies, and briefly doctors recommended delaying introducing milk to infants. (This advice has also changed.)
I only ask because it seemed to have been general knowledge that this was impossible / couldn't be done up until recently. As a outsider looking it, it seems quite obvious, but that's just due to naivete.
The original trial (I believe) came from a study that saw a certain Jewish community that eats a lot of powdered peanut, had a higher incidence of children losing their nut allergies. So the environment helped to prime these children.
My kid has allergies, and over the last 2 years we've seen the advice change rapidly - from initial suggestions to keep him away from anything that might cause him hives (soft play centres etc) to now where they encourage that (though obviously we still keep him away from eating allergens.
He had a laundry list of allergies that he responded to on his skin prick test last year, but his results yesterday were so much better - with the possibility that he only has 4 core responses left (peanuts, sesame, milk, egg) - with time still to lose those over time (he's only 3). We've been giving him loads of probiotics, namely Water Kefir - but no idea if he would have grown out of them anyway.
Happy to have a stab at any questions people might have - but I'm no expert, just a (reasonably) well read dad - my wife know far more than me about this.
1) Your body "sees" this, meaning it has antibodies that react to it
2) Cells whose antibodies are activated replicate, as they are recognizing something that is, to the body, presumably foreign and bad
3) Because you now have more cells after the originals replicated, the effects of the allergy worsen as you are now more reactive than before
I'd be interested to see some tests on this. I have a few hypothesizes that we could test:
1) If the children are still reactive to immunological tests (Meaning they still have the antibodies!), are those antibodies being blocked by another compound, another cross-reactive antibody? Another idea is that the actual immune response to antibody activation (Recognizing peanuts) might be handled differently within the cells that produce the actual response to the allergen (Swelling and stuff).
2) If the antibodies no longer exist, I would start looking in the areas where immune cells develop to see if cells producing reactive antibodies to the allergen are being killed off during development (This process is also why you don't kill yourself with antibodies recognizing yourself). If that isn't the case we need to track individual immune cells over the course of treatment.
The immune response to IgE binding is intense. Allergic reaction is an IgE response to a harmless antigen. However, IgE can be downregulated by repeated exposure to the antigen in question. If the body uses IgE too much (eg. from repeated exposure), it starts to replace IgE antibodies with the more subtle IgG antibodies.
The immune system is very fascinating really. IgE might be the key to effective cancer immunotherapy. Imagine if we could program your immune system to fight a cancer as intensely as it fights a pollen grain or peanut in an allergic individual. There is a lot of research in this area these days.
Thanks for clarifying that.
http://www.npr.org/sections/health-shots/2015/01/12/37566392...
https://en.wikipedia.org/wiki/Mithridates_VI_of_Pontus#Mithr...
For you, I would say visit your friends with cats often, at first taking an allergy pill before hand. Continue with frequent visits and cutting the dosage down. After you cut out the pill completely, make sure to continue to visit.
https://en.wikipedia.org/wiki/Mango#Potential_for_contact_de...
Before my dog was getting a mix of dry and "wet" food, from various companies, and occasional scraps from the table. Currently we only feed him dry food from Orijen, and plan on introducing some other "wet" food soon. He's also getting a good quality bones with a lot of bone marrow, and about once a week some boneless sardines in olive oil.
The reduction in shedding going from kibble that's primarily rice and corn to something that's actually nutritionally appropriate ingredients for a dog/cat was astounding (but should have been unsurprising).
My understanding is that pet allergies are generally allergies to the shed hair and skin, so a healthier diet may have reduced that significantly.
(For anyone curious, a basic analysis of a "cheap" food: http://www.dogfoodadvisor.com/dog-food-reviews/alpo-dog-food... And a basic analysis of a "good" food: http://www.dogfoodadvisor.com/dog-food-reviews/acana-singles...)
She stopped eating peanuts for about a year, then gradually found she was capable of eating them again (her favorite candy was Reese's peanut butter cups, so a heartbreaking year that was). My belief is she is more cautious on the volume and frequency of her consumption now, but is otherwise unrestricted.
My guess was always that she must've had some low-grade infection (viral or otherwise) and the response was also broadly interacting with the proteins in peanuts.
The immune system isn't a designed system, it's a series of responses (and the ability to generate new response) that we broadly call a system because the net effect is as if there were some dynamic thing protecting us. Sometimes it just does its thing without regard to the segmentation faults it creates.
My anecdote: our daughter was diagnosed with a peanut allergy at ~7 months of age. She developed hives after eating some peanut butter and we confirmed the allergy at our allergist's office with a skin test. We were told to give it another shot in ~5 years, but to avoid all nuts and carry an epi-pen in the meantime.
But just about a year later after an insurance change, our new pediatrician encouraged us to do another test with our new allergist. A blood test came back negative, and the ultimate test - eating increasing amounts of peanut butter in the allergist's office over a couple of hours - was fine.
edit: one study citing a need for more data: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879010/
another old article (2011) on the Hygiene Hypothesis: https://www.nature.com/nature/journal/v479/n7374_supp/full/4...
I feel like I have to throw away almost all advice they give us about kids these days. These types of things do a lot to undermine the advice of doctors.
The latter by the way led to a dramatic increase in incidents of Sudden Infant Death Syndrome causing us to roll out the "back to sleep" movement.
Many still disapprove of sleeping next to your baby despite it being as safe - safer in some instances - than sleeping in a crib and providing a protective effect against SIDS via the parents breathing/heartbeat as rhythm keeping and carbon dioxide that triggers regular breathing.
You basically have to take all parenting advice (even from a doctor) with a grain of salt and at the end of the day do what you as the child's guardian feel is best, especially because no one style or technique will work for all children.
And I use "feel" explicitly because often on more subtle issues there wont be a clear answer, even from your doctor.
I personally think that we will look back at the symbiotic relationships that bacteria provide, and be amazed by the way we currently live - with hand sanitisers, and even antibiotic dish soap - plus antibiotics in our meat and water... Sure we will look back on this time in the same way we look at Romans and lead water pipes.
I would think that it is transferred to the child at birth. Some factors that could lead to a higher incident of peanut allergies if this bacteria is vital to preventing it:
- Child was delivered via cesarean w/o a vaginal swab transfer. The rate of c-sectons has certainly increased quite a bit in the last few decades.
- The Mother did not have a health population to begin with.
- The use of antibiotics that could wipe these strains out. Either in the mother prior to delivery or in the child after being born.
- lack of introduction through other sources (some yoghurts and cheeses)
The importance of this work is that with the simultaneous introduction of this bacteria the effect is maintained for years. The bacteria plays a important role in allowing the body to retain the immunity.
"Moreover, because there was no convincing evidence that allergen OITalone was effective in promoting sustained unresponsiveness at the time our randomized controlled trial (RCT) was designed and initiated, we elected to undertake a clinical trial evaluating whether coadministration of Lactobacillus rhamnosus CGMCC 1.3724 (NCC4007) and peanut OIT can induce sustained unresponsiveness to peanut among children with peanut allergy (Australian New Zealand Clinical Trials Registry ACTRN 12608000594325, 25/11/2008). This probiotic was selected based on its demonstrated tolerance-promoting effects, including induction of regulatory T and TH1 cytokine responses."
I do like lobster when the price is reasonable. What is true is that it's very delicate so it's really wasted in things like lobster mac and cheese.
http://www.npr.org/sections/thesalt/2015/03/26/394339284/how...
Food fashions aren't always rational though. It seems to have become popular largely when people from New York and DC started vacationing up in New England in the 1800s.
Veblen goods are goods that people buy to signal their higher status.
(No opinion on whether lobsters outside of New England are Veblen goods. Am vegetarian)
It's not clear that Giffen Goods actually exist.
Caviar is still tasty, but not fundamentally different from, say, peanut butter. It's something you spread on bread. I don't think I'd bother with it.
If you do get some, try putting sliced, hard-boiled egg in a sandwich, caviar on top of the eggs. That's a great combination.
Crab is where the flavors at!
At the end of the day, I would take oysters over both because I prefer salty to sweet. A fresh local oyster from the water that morning either raw or lightly steamed is delicious.
I started my food side project https://bestfoodnearme.com with the idea in mind that I can catalog dishes at restaurants based on allergies, gluten free etc. Allergic reactions are a very scary thing especially with small children.
Anyway I've a severe allergy against figs and hope I can one day eat them again.
I have never heard of these kind of bacteria and thought that probiotics is a scam in that it replaces your gut bacteria with ones that are genetically modified so that you "feel" bad without re-consuming them. I think it sounds crazy, while being in the technically possible realm with no law against that.
The control group only saw one person's allergy diminish during the initial treatment period.
I'll freely admit I don't have a background in statistics or clinical trial design, but it seems to me with that significant of an effect you can be fairly confident in the results even at that trial size.
If we were talking 8% to 4% in 24-person groups, sure, one extra person having a positive result could be random chance. We're talking 82% to 4%. It seems pretty unlikely that 19 people all randomly has a positive result unrelated to the treatment.
How big do you think these trial groups need to be to confirm the effect of the treatment, if this isn't good enough?
Her clinic is relatively unique, in that it will be offering multi-allergen rapid desensitization. Using this procedure, a person can be desensitized to multiple allergens simultaneously, in as little as three months. She can treat milk, egg, wheat, soy, peanut, tree nut, fish, and shellfish allergies.
[0]: http://wmboit.com
It used to be a healthful breakfast given its balanced nutritional profile per one cup: 150 calories, 8 g of fat (5 g of which saturated), 5 g of carbs, and 13 g of protein while supplying 1/3rd of your daily calcium need.
In Serbia we have different types of yogurt some more thick (the westernized with flavor), yet some runny/less thick. But sour milk (kiselo mleko for us) is always of same texture and we eat it with a spoon. So, my question is - do Bulgarians drink their yogurt or do they eat it with a spoon?
1. Heat milk and milk cream (mostly milk cream), let cool, add yogurt culture
2. After yogurt is set, add water and churn
3. Extract the butter that you get from churning, drink the leftover buttermilk :-)
4. Heat the butter till it's ghee
But what I meant is that ghee is not made with yogurt and not solely from fermented milk - and ghee doesn't have to be cultured either (most brands available in US stores are not). Again, my point was, that for fermented milk to be called "yogurt," it needs to have a particular Lactobacillus profile, which is not traditionally available in India. Nowadays, maybe you use the imported starter cultures just like Japan, USA, and EU does.
Please do :-)! The butter by itself is quite tasty; more tangy than store-bought butter and delicious when whipped with powdered sugar then spread on bread.
> it needs to have a particular Lactobacillus profile, which is not traditionally available in India
Sorry, do you have a source for this? I was unable to find anything. I don't think it would've been too difficult for yogurt cultures to diffuse gradually from Bulgaria to India in ancient times. There were plenty of traders and conquering armies going back and forth. Yogurt has been in India for thousands of years.
With regard to yogurt cultures used in India, I only found the following: "In India, a combination of "Lactobacillus bulgaricus" and "Streptococcus thermophilus" is used for commercial production." [1]
[1] http://www.indiacurry.com/faqmilk/mfaqdahichemistery.htm
Every country has some regulation on what should be marketed as "butter," "cheese," "yogurt" so that consumers are not deceived. For example, in Bulgaria, recently there's been "butter" on the market with 70% hydrogenated palm oil! If there's no precise definition of what "yogurt" is, kefir, butter milk, and lassi can be sold as yogurt then - they are fermented dairy products as well
Here's the definition of FDA although it's possibly the vaguest: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFR...
In Bulgaria, for example, there's strict standard, which even limits the types of containers that can be used to sell yogurt (as some may alter the taste or leach chemicals).
I know that there's EU regulation on yogurt as well, but I'm not able to find it, unfortunately.
In the US, I think this is being marketed as "Greek yogurt." (I don't like yogurt so no first hand experience, but in the last few years I've noticed many brands being advertised as "Greek", and as being more tangy and possibly more healthy/"natural")
I don't think either process affects acidity.