Preventing Allergies

The cause of allergies and autoimmune degenerative diseases is inflammation.

As a scientist, I am concerned with how the body works at the molecular level. I try to understand how molecules of cells interact to cause disease. So if you tell me that you have an allergy, I want to understand how you became allergic and I am much less interested in how you avoid triggering your allergy. If you say that your allergy is triggered by ragweed pollen, I want to know the shape and structure of the proteins or carbohydrates of the pollen that actually come in contact with receptors on the surface of your cells and trigger the allergic response, but I also want to trace those interactions back to the original events that started the allergy.

Allergies are mistakes of your immune system. Your body should learn to ignore common food and environmental molecules as it ignores itself. There is an elaborate system used by cells of your body to disassemble and display fragments of dangerous pathogens on the surface of cells for evaluation by the immune system. Inappropriate display of innocuous or self molecules is part of the problem in allergies and autoimmunity.

Ragweed pollen, for example, will cause no reaction unless pollen proteins bind to antibodies (IgE) held in receptors on the surface of mast cells. We know that ragweed pollen binds to anti-ragweed antibodies on the surface of mast cells of allergic individuals and triggers the release of histamine and other molecules that give the symptoms of allergy. That’s why you take antihistamines to remediate the allergic symptoms. The first questions are what are the ragweed molecules to which the antibodies bind, i.e. the ragweed allergens and why is this allergic person producing anti-ragweed antibodies?

We know that the ragweed allergens are common pollen proteins, but why are they particularly prone to producing allergies? I tried to figure out this riddle by asking if there is something about these proteins that make their transport into cells more likely. I had just discovered that a particular amino acid sequence, a triplet of basic amino acids, lysine or arginine, resulted in transport of proteins into cells. This triplet that provides binding to heparin is found, for example in the nasty HIV protein, called TAT that moves on heparan sulfate proteoglycans (HSPGs) from infected to uninfected human cells and paves the way for the spread of infection. This triplet is also found in heparanase, that is first secreted by cells in an inactive form, is brought back into cells by binding to HSPGs, is activated by partial digestion and resecreted for action in the extracellular environment. This heparin-binding triplet can also be added to other proteins, e.g. the fluorescent jellyfish protein, to transport those proteins into cells.

Examination of ragweed pollen and subsequently dozens of other common allergens revealed that each one (or a close relative) possessed the unusual heparin-binding triplet of basic amino acids. The basic charged character of these sequences also determined that these parts of proteins would be present as accessible coils on the surface of the proteins. It is interesting that people suffering from the autoimmune disease of lupus produce antibodies to most of the proteins found in the nucleus of their cells. These nuclear proteins bind to nucleic acids, that mimic the structure of heparin and in many cases have triplets of heparin-binding basic amino acids. Thus, it appears that allergenic proteins enhance the chance of uptake by cells that can display them to the immune system, because of their triplet heparin-binding domains and the immune system subsequently produces antibodies that bind to other regions of the protein allergens. This explains how the antibodies are produced to these allergens, but it does not explain why some people produce antibodies to environmental antigens and healthy people do not.

Allergic people readily expand their allergies to include new allergens. What is it about these susceptible people that makes them allergic? I think that the answer is inflammation. Inflammation leads to a disruption of normal production of heparan sulfate proteoglycans and as a consequence to a change in how external proteins interact with cells involved in processing antigens for presentation to the immune system. This means that people with chronic inflammation, also called the metabolic syndrome, are not only increasingly susceptible to diabetes, arthritis, heart disease, etc. but they are also at risk for picking up new allergies. This also suggests that an anti-inflammatory diet and lifestyle changes would be of great benefit to those with allergies. Unfortunately, because of immunological memory, it will take years to deplete the population of antibody secreting cells that provide the basis for a specific allergy and during this depletion time, the allergen would have to be scrupulously avoided. It might also mean that autoimmune diseases such as type I diabetes might be treated by depletion of anti-beta cell antibodies and their secreting B cells along with a shift to an aggressively anti-inflammatory diet.

It is my belief that many of the genetic components of allergies and autoimmune diseases would not be experienced in the absence of chronic inflammation as a precipitating condition.