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Peanut allergy may start in the gut – opening up new ways to tackle it

Severe food allergies can be terrifying, both for the person affected and their loved ones. Allergies are increasing and affect between 3% and 6% of the population. But science has yet to fully grasp the reasons why. One theory – which appears to be backed up by the evidence of a new study – is that the answer lies in the human gut.

More specifically, the antibodies produced in the human gut. Antibodies are an important part of our immune system that help us recognise and eliminate “foreign” antigens (proteins on the surface of a substance that triggers an immune response). Foreign antigens are found on viruses, bacteria and other things that may cause us harm, as well as the food we eat.

Antibodies are made by B-cells (a type of white blood cell called a lymphocyte) which mature in the bone marrow before migrating to other parts of the body. Then the B-cells make antibodies in response to foreign antigens they meet. This new study suggests that B-cells can influence whether an immune response is too “strong” against peanut antigens, by producing too much of a type of antibody that encourages severe allergic reactions, and not producing enough of the antibodies that keep our bodies from overreacting in this way.

Antibodies and allergies

Humans produce five different types of antibodies or immunoglobulins (Ig) – IgA, IgM, IgG, IgD and IgE. IgE, which is known as the “allergy antibody”, mainly protects us against parasite infections, but it also helps to cause anaphylaxis – a serious, rapid allergic reaction that can cause an itchy rash, throat or tongue swelling, shortness of breath, vomiting and ultimately death. Anaphylaxis can occur in people who are allergic to peanuts as well as other foods.

IgE is usually the least abundant type of antibody, at only 0.05% of antibodies in the blood, but it can cause the most powerful of immune reactions. IgG is the most common antibody in the blood, at around 75%. IgG helps other immune cells to clear away dangerous material.

Researchers sequenced all the Ig antibody genes from B-cells in tissues from different organs of 19 people with a peanut allergy and compared them with those of non-allergic people. The results showed that more IgE-producing B-cells reside within the gut of those with allergies, compared with those who don’t. There were roughly equal numbers of B-cells in the blood and bone marrow of both groups, so it is the gut-residing B-cells that are different.

The report found that non-allergic people make more of the common IgG-type antibodies in response to peanut proteins than allergic people. These antibodies can neutralise the negative effect of the “allergic antibody” and therefore it may be that people with peanut allergies may not only produce too much IgE, but may not produce enough IgG.

Read more: Curious Kids: if you have lots of the thing you're allergic to, does your body get used to it?

The research shows that gut tissue is a likely place for the development of the IgE allergy antibody in people who are allergic to peanuts. This makes sense because the gut is the site of vast quantities of foreign proteins, in the form of microflora (the microbes that live within us) and in the food we eat. But usually, people’s immune systems do not react to their gut contents because they have formed “tolerant” immune responses early in life.

The timing of first exposure to proteins (of microbe or food origin) may be influencing how much IgE and IgG antibodies are made. So if more allergic antibodies are made, then it renders that person “sensitive” (and more likely to be allergic), rather than tolerant. This is why immune tolerance training through exposure to antigens while in the womb and early life, through proteins in the mother’s diet and her intestinal microflora, is particularly important.

An increasing body of evidence supports the hypothesis that early antigen exposure increases tolerance and lowers risk of childhood food allergies and other diseases. Historically, pregnant women were advised to limit their intake of peanuts, as it was initially thought that consumption during pregnancy could increase the risk of an allergic child.

Eating nuts during pregnancy

Evidence now suggests that avoiding nuts during pregnancy may prevent the foetus being exposed to nut antigens in the womb, where tolerance starts to be developed, and therefore increase the risk of an allergic child.

This hypothesis is also supported by recent evidence showing that intestinal microflora (of both mother and child) plays a major role in immune tolerance development, both while in the womb and in early life. So eating nuts during pregnancy, or when breastfeeding, may reduce the risk of a child developing an allergy.

The new study also discovered that many people share similar peanut-reactive IgE DNA sequences, which was surprising as one person’s antibodies are usually different from another’s.

This suggests that IgE antibodies in different people recognise peanut proteins in a similar way, which could help scientists in developing drugs to neutralise the “allergic antibodies” that cause anaphylaxis. Such drugs could be taken before or after exposure to lessen the allergic reaction and prevent anaphylaxis. But it may be several years before this type of treatment is available.

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