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 results.
Of the four subclasses the most commonly tested are IgG1 and IgG4, as these are produced in response to food antigens and can be used to identify sensitivities. IgG1 antibodies are ‘first responders’ and as such reach new food antigens by joining the antigens and forming complexes.
These complexes are destroyed by immune system cells called macrophages. IgG1 antibodies can additionally activate further immune reactions such as the complement cascade and inflammation.
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
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 sensitivity. 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, 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.
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