Allergy: Our Understanding of Immune System Tolerance is Evolving

So what is allergy? You know, there's been a long standing belief that allergy is just kind of inborn. We have the genes for allergy, eczema, asthma. It just occurs as atopy, as a consequence of the genes of the infant, of the child. But is that really true? Is it just strictly an inborn, hard, fixed genetic determinant, or are there environmental factors that really mitigate the way the genes are expressed? Let's say just a quick word about allergy in terms of its immunological explanation. As you probably know, the immune system is this complex system of cells that are there as a kind of a community to protect us against all sorts of hazards in the outside and inside world. And we could just for simplicity, say that we break down the immune system into two components. One would be called the kind of air to air missile system, the antibody system, in which B cells produce antibodies that go out and lock onto foreign invaders and glue them together or get rid of foreigners. And the other is the hand to hand combat T cell part of our immune system that's involved with actual battle in our blood system, so called innate immune system that can bleach foreigners to death and through a chemical process that releases hypochlorite and phagocytizes by putting their AR around cells and hugging them to death. So we've got these two components of the immune system and within that then there is even further differentiation into what are called the T cells that are involved with what are called TH1 inflammation and the T cells that are involved in what are called TH2 kind of immune quiescent effects in allergy. Now to make this long standing discussion a little bit concluded, it's a TH2 dominant effect. So you get this imbalance of the totter of immunity of these T cells that are involved with cell mediated defense. So then how does the body become allergic? It's by certain substances that that individual is exposed to being seen as foreigners. And what does a foreigner mean? It means that it's someone you're not familiar with, right? Someone you have no background with, you have no previous experience with, and therefore your body may be poised then to react xenophobically to that foreigner and react violently. Which allergy with a dominant TH2 personality. So if we take all of that long winded kind of description of allergy and immune function, how does that translate into things like peanut allergies or cow's milk allergy, or egg allergy that are often seen in infants? And that's a fascinating part of the evolving story for which we're learning that there's something we can do. So I'm now quoting from a recent article in the Lancet Medical magazine. This is actually the January 23rd issue of 2017 entitled Another Step towards Prevention of Food Allergy. And in this article they go on to talk about the solids Timing for Allergy Research study or so called STAR study. They talk about the hens egg allergy prevention study or the HEAP study. And they talk about the fact that there is this inquiring about tolerance study, eat study that have all looked for ways of neutralizing egg allergy in infants. And then they go on to say, but the best study of all is the one that was just published in our issue of the Lancet, which is a study by Otsuma Natsumi et al. That really looks at how to neutralize egg allergy in infants. And this is entitled the Two Step Egg Introduction for the Prevention of Egg Allergy in High Risk Infants with Eczema. A randomized double blind placebo controlled trial in which they were able to demonstrate the very significant reduction in hen eggs allergy and eczema in infants that already had shown an intolerance to egg and had this immune reaction that we call allergy. And what they did is introduce cooked egg at very low quantities to these infants that were egg allergic to try to neutralize their immune system. And what I would say is to familiarize their immune system with these egg proteins so that they became not foreigners, but they became recognized friends of the family. And by introducing this approach, which was to start with a very low dose of cooked egg protein, they were able to show a dramatic improvement in egg tolerance. In fact, it went from 38% of the kids in the placebo group being egg intolerant in this egg neutralization group down to as low as 8%. So it's a more than four fold reduction. And they go to say that introduction of the heated egg in a step white manner along with aggressive eczema treatment was found to be safe and efficacious way to prevent hen egg allergy in infants. So it's not just solely that we're inborn to be allergic. There are other factors that are related to the tolerance of our immune system for things that it's never seen before. Now let me ask the question then, could you then prime the tolerance of a system by regulating this th2th1 balance and infant then to have an immune system that was a little less hypersensitive to foreign proteins? And that takes us to a Very interesting paper that appeared in the New England Journal of Medicine. This was in the December 29 issue of 2016 under the title Fish Oil Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring. And in this case, the fish oils were given to the mother in a supplemental dose 24 weeks of gestation to receive 2.4 grams of these long chain omega 3 fatty acids supplement daily. And what they found is by giving the mother immune stabilizing nutrients that their offspring had a significant reduction in the incidence of asthma or wheezing, suggesting that it's not just the inborn errors or the inborn nature of the genes of the infant, it's also the environment in which those genes were nurtured and the environment post delivery that they're exposed to. So now we have a lot more variables that we could use to reduce the ever increasing exposure of allergy and eczema in our population. Then you might say, well, if that's true, then could you take things like peanuts that are very serious allergic producing foods in some children and reduce their allergic potential? And here we go to two major medical journals, the Journal of the American Medical association and the New England Journal of Medicine just within the last couple of years. So let's talk about the JAMA paper first, prospective study of peripregnancy consumption of peanuts or tree nuts by mothers and the risk of peanut or tree nut allergy in their offspring. Now what does this mean? It means the mothers voluntarily consumed more peanuts or tree nut foods over the course of their pregnancy. And then the question is, could they then familiarize their fetus with the appearance of these proteins so that they would be less not allergy sensitive when they were born. And the results are quite amazing actually when you look at the outcome among mothers with peanut allergy. Higher peripregnancy consumption of peanuts was associated with a lower risk of peanut allergy in the offspring studies supporting the hypothesis that early allergen exposure at low dose increases tolerance and lowers the risk of childhood food allergy. Now this goes back, way back to Herbert Wrinkle and the whole basis of food allergy and desensitization and neutralization, titration. That's the foundation of some forms of what we would call allergic desensitization that has been practiced now since the early 1960s, but never really got foothold in traditional allergy and immunology, but is now being seen to be much more science based. Another paper that I mentioned, the New England Journal of Medicine, this is 2015 in the February, February 26 issue is entitled Randomized trial of Peanut consumption in Infants at risk for Peanut Allergy. And again, what they find is that the early introduction at low levels of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune response to peanuts. So it's like an immunization, low dose neutralization, intolerance rather than just a load of foreigners at the door that create a hostile response of the immune system. Now, if this is true, then you might say there could be other things that we could do to make the immune system which is in the gut. As you recall, over 50% of our immune system is surrounding our gastrointestinal system, the so called gastrointestinal associated lymphoid tissue. And therefore, could you desensitize the gut immune system by certain types of interventions or agents? And yes, there are a couple that have been described. One is certain probiotics. This is a paper that appeared in Molecular Nutrition and Food research back in 2013 showing that the probiotic VSL number three was able to ameliorate food allergy and inflammation. This is in a mouse model of peanut sensitization through introduction of the proper regulatory T cell personalities in the gut immune mucosa. Meaning here you're balancing the immune system by having friendly bacteria that speak to the gut in such a way as to desensitize to foreign prote. Well, are there other things you can do? Well, yes. Remember years ago an observation was made that kids that had less eczema and allergy and atopy were often kids in developing countries with a lot of worms. And so people started asking, well, hold it, is there something about worms that desensitizes the gut immune system to food allergens? And the answer is yes. There's a very large body of literature showing that helminth induced immunoregulation can reduce allergic response to foods, meaning that the worms have on their surface. Remember, worms have this kind of slimy stuff, this mucus like stuff on their surface that are actually immunoregulators that regulate the immune system to be less sensitive than to foreign molecules, to different molecules in the food. So here's a paper that just appeared in the Journal of Immunology about enteric helminthin infection protection against allergic responses to dietary antigens like peanuts. So what I'm trying to say to you is this is an extraordinary story of back to the future because there were early investigators like Theron Randolph and like Harvey Wrinkle and Coca and others who really were talking about neutralization titration against food allergens, which was seen to be completely antithetical to the traditional allergist at the time. You want to remove all exposure, but now we're talking about low dose titration to neutralization to desensitize the immune system and to make what was a foreigner appear as a friend of the home. And as a consequence then creating tolerance rather than intolerance, which we call allergy. So it's an extraordinary next chapter forward in which we recognize that sometimes introducing not the perfect environment for the infant, but an environment that is low dose, challenging their immune system, allows their immune system to gain tolerance to that factor. And it even can go through the mother with regard to priming her immune system, like the supplementation with omega 3 fatty acids during pregnancy. Very exciting story.