IgG4 and why?

The intolerance indicator that’s more accurate

What's IgG4 and why do we use it?

Immunoglobulin G (IgG) is a type of antibody found in human blood. The antibody has four subclasses (1-4) and make up an important part of the body’s immune response.

We test for raised IgG4 levels when identifying immune-mediated intolerances. There are a range of IgG tests available to health professionals all over the world, some testing all subclasses and others testing one subclass but there is still debate about which is the most effective.

The subclasses 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 and therefore produce a high rate of false positives.

The results provided by testing of these antibodies are commonly used to adapt an individual’s diet through elimination or optimisation.

Scientific Research

Here at Lifelab Testing, we are constantly updating our practices to ensure we follow the most up-to-date research. Here are the latest scientific papers from 2000 to now.

Why we only test IgG4

We test for IgG4 over IgG1-4 as this ensures a reduced number of false positives in the results and therefore offering you the most defined test.

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 and only consists of 1-4% of the food-specific IgG antibodies present.

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 avoiding too many foods unnecessarily, therefore improving patient compliance and outcome.

IgG4 Antigen Complex

If the body is continually exposed to a particular 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 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:

IgG4 - The Marker of Chronic Food-Immune Reactions

As a result of this, the complexes will get larger. From then, these larger complexes can activate the complement cascade, initiating inflammatory responses in the body, and becoming 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 symptoms. This sequence of events is thought to be the most common way individuals develop adverse reactions to foods that they consume regularly.

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 unnecessary food eliminations.

The IgG4 antibody is a more clinically applicable marker of chronic food-immune reactions and 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 provide a high rate of false-positive reactions.

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