Why IgG₄?

It's more accurate: simple.

IgG₁ and IgG₄ – The Physiological Process

Testing for IgG₄ over IgG₁ or total IgG is an advantage, as it leads to a reduced number of false-positives and allows for more targeted, relevant results.

Of the four subclasses the most commonly tested are IgG₁ and IgG₄, as these are produced in response to food antigens and therefore can be used to identify intolerances. IgG₁ antibodies are ‘first responders’ and as such reach new food antigens by joining the antigens and forming complexes.

These complexes are quickly destroyed by immune system cells called macrophages. IgG₁ antibodies can additionally activate further immune reactions such as the complement cascade and inflammation.

Why Do We Test IgG₄ Over Total IgG Or IgG₁?

Food allergies, intolerances and sensitivities are becoming more topical in a variety of sectors in the healthcare industry. It is a constant talking point for both health professionals and their patients. Nutrition as a topic and, more specifically allergies, intolerances and sensitivities, are getting more coverage than ever in the media. This is helping spread awareness about potential symptoms and the benefits of testing.

IgG₁ and IgG₄

In order to test for immune-mediated intolerances specifically, testing for IgG antibodies is required. Within the IgG class there are four IgG subclasses. There are a range of IgG tests, which are available to health professionals all over the world, some testing all subclasses and others testing one subclass but there are on-going discussions about which is the most effective. Of the four subclasses the most commonly tested are IgG1 and IgG4, as these are produced in response to food antigens and therefore can be used to identify intolerances. IgG2 and IgG3 are not generally produced in response to food antigens. The main difference between IgG1 and IgG4 is how they respond to food antigens. IgG1 antibodies are like ‘first responders’ and are produced in response to new food antigens whereas IgG4 antibodies are produced when the body is continually exposed to an antigen.

Therefore testing for IgG4 over IgG1 or total IgG is an advantage, as it leads to a reduced number of false-positives and allows for much more targeted, relevant results. It reduces the incidence of patients removing too many foods and doing so unnecessarily, therefore improving patient compliance and outcome. Basically, you are able to learn and understand the food items your body can tolerate, or, no longer tolerate and take steps to make changes with confidence.

IgG₄ Antigen Complex

If the body is continually exposed to a certain antigen, this could lead to a ‘class switch’ from IgG₁ to IgG₄ antibody production. These IgG₄ antigen complexes do not then activate the complement cascade. This is because complexes of IgG₄ and food antigens are very stable, and alterations in any sort of structure can lead to new antigen forms.

From this, IgG₁ is then produced to attach the IgG₄– antigen-complex. This in turn creates a whole new cycle, which goes like this:

IgG₁ (class switch) → IgG₄ → IgG₄-antigen-complex → modification → IgG₁ → IgG₄

IgG₄ - The Marker of Chronic Food-Immune Reactions

As a result of this, the complexes will get larger. From then, these larger complexes are able to activate the complement cascade, initiating inflammatory responses in the body, and thus are detectable through blood testing. The inflammatory response to a food is the main cause of symptoms in this type of food reaction resulting from food intolerance. These complexes can also be deposed in tissue or organs, leading to damage, which can cause uncomfortable and nuisance symptoms to an individual. This sequence of events is thought to be the most common way individuals develop adverse reactions to foods, which they consume on a regular basis.

IgG₁ antibodies show themselves to be more adhesive, and readily bind to any antigens. This increases the possibility of cross-reactivity and therefore the number of false-positive results in testing. This means that testing both IgG₁ and IgG₄ can lead to many unnecessary food eliminations. As an antibody, the IgG₄ antibody is a more clinically applicable marker of chronic food-immune reactions and of possible intestinal hyper-permeability. Between IgG₁ and IgG₄, IgG₄ measurements are less likely to produce false-positives on in-vitro tests. Similarly, when measuring all ranges of IgG, or total IgG, it is more likely that these will produce a high rate of false-positive reactions.