Diagnosing allergy is a subject that is very commonly misunderstood. One of the commonest misunderstandings concerns the role of blood tests in managing allergies. When considering the use of medical tests, there are several pertinent questions that need to be answered.
As mentioned in previous articles, allergic reactions can be mediated by different immune mechanisms. The most common type of allergic reaction is mediated by IgE antibodies, and therefore most blood tests for allergy seek to measure allergen-specific IgE. Most of these tests will also measure the total IgE level. There are several obstacles that developers of blood tests must overcome. First, IgE antibodies are mainly found on the surface of mast cells, and the amount of free IgE in the blood is miniscule, and might not truly reflect what is found on the mast cells. Therefore, extremely sensitive methods must be employed to measure these antibodies. These tests employ allergens that are bound to a solid phase to capture IgE antibodies in the blood sample. Anti-IgE antibodies are then used to detect these captured IgE antibodies, and the signal is amplified using enzymatic reactions or radioactivity. This amplification process increases the background noise of the assay, and greatly increases the chance of false positive results.
Second, these assays only measure the binding of IgE to the allergens on the solid phase. While IgE binding is the essential first step during an allergic reaction, it does not necessarily lead to the complete allergic reaction, just as a key that can be inserted into a lock does not guarantee that it can open that lock. Therefore, antibodies that are structurally similar to the antibodies that are being measured will also show up in the assay, but these cross-reacting antibodies might actually be specific for bacterial or other irrelevant antigens. This problem is extremely common in patients with very high total IgE levels, such as patients with eczema who has repeated skin infections. On average, there is a greater than 50% chance of a positive food IgE test result being false.
Studies in the 1970s found that IgG antibodies can also cause allergic reactions in rodents. Therefore, tests for IgG antibodies that bind to food were developed, because IgG antibodies are very abundant (several million-fold more concentrated than IgE) and hence very easy to measure with crude assays such as ELISA. However, IgG antibodies do NOT lead to allergic reactions in human beings. In fact, one of the mechanisms that the body uses to produce immune tolerance is allergen-specific IgG4 antibodies. IgG4 antibodies are immunologically inert, yet they compete with IgE for allergen binding, and since they exist at much higher concentrations, they can effectively block IgE-mediated allergic reactions. Accurate tests that measure allergen-specific IgG4 are useful in determining immunological tolerance, especially during desensitization therapy.
Despite their lack of effectiveness, IgG blood tests are still being heavily promoted for the diagnosis of food allergy and “intolerance”. Many patients have been misled by these tests into believing that they have multiple food allergies, and undergo unnecessary and even harmful food avoidance. More ominously, real food allergy remains undiagnosed, leading to fatal or near-fatal accidents. Any laboratory that promotes food IgG tests for diagnosing allergy is perpetrating healthcare fraud.
Specific IgE blood tests are useful when skin testing is impractical, such as when patients have active urticaria (hives) or other skin conditions, or if patients cannot stop antihistamine treatment. Only tests that have been validated, i.e. tests that have received FDA approval or clearance, should be used. Blood test results must be interpreted with care, and positive results should be verified by challenge testing unless there is strong clinical evidence to support the results. The level of specific IgE might be useful in monitoring the progression of food allergies, since a declining trend of food-specific IgE is a good prognostic factor for eventually outgrowing that allergy.
The most commonly used FDA-approved allergy blood tests include RAST, MAST, CAP, UniCAP and chemiluminescence assay.
Many laboratories performing non-validated blood tests claim that these tests can be used to identify food intolerance. Such tests typically test for dozens or even hundreds of foods using crude methods such as ELISA. Food intolerance is not a diagnosis, rather an umbrella term for any condition that produces symptoms due to food ingestion. Food allergy, for example, is a form of food intolerance. Other examples include enzyme deficiencies that can lead to indigestion or malabsorption of certain nutrients, pharmacological effects of food chemicals such as caffeine etc.
Since none of these conditions, with the exception of food allergy, involve food-specific antibodies, antibody blood tests have no role in making diagnosis. Any laboratory that claims that a blood test can be used to diagnose food intolerance is committing healthcare fraud.