When immunity goes crazy or Allergy from the perspective of epigenetics

A speck of pollen, a mite, a few cat hairs, or even milk protein – none of these things threaten the body in the slightest. So why does the immune system sometimes go crazy and attack them as if they were life-threatening invaders? There are a number of reasons, but recent research shows that epigenetic reactions, which alter the activity of certain genes in our DNA, play a big part in allergies.

An allergy is an exaggerated reaction of the immune system to an otherwise completely harmless environmental substance. There are several types of allergies, most of which (also known as atopy) are associated with the immunoglobulin IgE. These include most types of asthma, allergic rhinitis, allergic conjunctivitis, atopic eczema and food allergies.

IgE is an antibody secreted by immune B-cells. Their activation also requires the activation of another type of immune cells, called T-cells, especially Th2 lymphocytes. IgE antibodies then bind to mast cells, which secrete histamine, and it is this substance that is the actual cause of allergic manifestations. In addition, activated T cells secrete substances called cytokines that promote the progression of inflammatory processes.

In addition, there are types of allergies that are not related to IgE antibodies. These include some types of asthma and, in particular, contact dermatitis, in which the skin is irritated by contact with certain substances, such as allergies to metals and jewellery. In this case, there is only an activation of T-cells, which start secreting inflammatory cytokines. These then cause other types of immune cells to enter the tissue, which then cause irritation and damage.

A completely harmless enemy

But how does the immune system go crazy and start attacking completely harmless substances? A high proportion of genetics is often mentioned, but this does not add up when you look a little more closely. It is true that if a parent is allergic, the risk of allergy in his or her offspring increases significantly. But then how do we explain the fact that the incidence of allergies has increased so dramatically in recent decades? Where would children who have no allergist among their ancestors come to them?

Therefore, environmental and lifestyle factors certainly play a major role, but they also have epigenetic effects – they trigger biochemical reactions in the body that can fundamentally change the activity of many genes in our DNA. The high prevalence within families is then due not only to the same external factors that affect parents and children (diet, environmental toxins), but also to the fact that a large part of epigenetic changes are hereditary.

Because the formation of an allergic reaction is a relatively complex process – the number of cells involved is quite large, each of which must go through a process of formation, differentiation and activation. The number of genes that regulate these processes is so large and there are therefore many ways in which these processes can be influenced by epigenetic reactions.

From an epigenetic point of view, allergy is primarily associated with changes in gene methylation – so much so that the methylation patterns can predict allergy before it occurs. For example, 81 DNA regions were found to have different methylation patterns in children with atopic asthma, and as many as 96 differently methylated regions in children with food allergies. These included genes involved in T-cell maturation, regulation of immune function and inflammatory processes.

In most cases, these methylation changes are present from birth – this means that the allergic child has either inherited them from one of the parents or they have arisen during the child’s intrauterine development.

Factors influencing the development of allergies

There are many causes and risk factors for allergies that are somehow related to epigenetics. Here are some of them.

Too much purity

Recently, the so-called hygiene hypothesis has become very popular, which states that the reason for the increase in allergies in recent decades is the extreme emphasis on cleanliness. It turns out that contact with various types of micro-organisms in early childhood, including faecal bacteria from, for example, livestock or soil bacteria, is important for the proper development of the immune system. Contact with these microbes is closely linked to the development of the gut microbiome, and it is the disturbance of this balance that increases the risk of allergies.

Too few parasites

According to some theories, the increased incidence of allergies may also be linked to the fact that most parasite species have been eradicated in Western countries. In fact, the immune response that occurs in the body when contact with an allergen occurs (i.e. activation of T-cells, mast cells and production of IgE antibodies) is similar to that by which immune cells attack multicellular parasites.

Active and passive smoking

Smoking is one of the very significant epigenetic factors that affects DNA methylation. Disruption of methylation patterns subsequently leads to an increased risk of a number of diseases, including allergy and asthma. Moreover, these are changes that can be inherited. It is particularly dangerous if a pregnant woman smokes – then not only her child but also her future grandchildren are at increased risk of developing allergies.

Air pollution

The risk of allergies is also significantly increased by living in a polluted environment. This is because air pollutants, especially sulphur and nitrogen oxides, ozone and fine dust particles, significantly increase the methylation of the FOX3 gene in some immune cells. These changes are very common in children with asthma. Polluted air is not only a threat to those who breathe it – the risk of allergies is also increased in children of mothers who have been exposed during pregnancy.

Medications and infections

Frequent use of antibiotics and antipyretics also increases the risk. However, certain viral and bacterial infections, such as golden staph, can also play a role.

Stress

However, the influence of psychological factors, especially stress, cannot be excluded. This was evident, for example, in the extreme snowstorm that hit the Canadian province of Ontario in 1998. Scientists examined the DNA of children who were pregnant during this event and found different patterns of gene methylation, including in T-cells. Because of this, there was a much higher incidence of several diseases among these children, one of which was asthma.

Breastfeeding benefits

Breastfeeding and later consumption of unpasteurized milk also has a positive effect. On the other hand, the early inclusion of foods that are common allergens in infants’ diets has not been shown to promote the development of allergies. Rather, for example, the avoidance of cow’s milk and the use of hypoallergenic infant milks may promote the development of allergies.

The association of allergies with high consumption of so-called methyl donors during pregnancy is interesting. These are substances that are absolutely necessary during this period for the proper course of methylation processes – the most famous of them is folic acid. If they are not sufficient in the diet, this can lead to serious developmental damage to the fetus. However, it turns out that if there is too much of it, i.e. if, for example, a mother consuming a diet high in folic acid also takes high doses of supplements, this can lead to the development of allergies.

Dietary supplements for allergies

Dietary supplements are never likely to be as effective as, for example, antihistamines or corticosteroids, but unlike them they have no adverse side effects. In addition, the following may act directly on the cause of allergic problems due to their epigenetic effects.

Baikal coneflower – the substance baikalein contained in this herb has a rather pronounced anti-allergic effect, it mainly inhibits the production of histamine, and thus reduces the intensity of allergic symptoms. Moreover, it acts very quickly – for example, it is effective if given 48 hours before encountering the allergen, which can be particularly useful for pollen allergy sufferers.

Rosemary – the extract from this plant causes cell death of activated T-cells, thus targeting directly the cellular mechanisms of allergy. It is very effective in alleviating allergic rhinitis, watery and burning eyes after about three weeks of use. However, it also effectively relieves the symptoms of asthma.

EGCG – epigallocatechin gallate contained in green tea also has an anti-allergic effect.