By Dr. Paul Ehrlich & Henry Ehrlich
The long-time quest for a better blood test for food allergies may be closer than we thought. A letter in the Journal of Allergy and Clinical Immunology by six UK researchers headed by Alexandra Santos, MD, PhD, describes a study of the blood of children 73 of whom were diagnosed peanut allergic, 60 who were peanut-sensitized, and 41 non-allergic. Samples were subjected both to basophil activation tests (BATs), which are known to be highly predictive of allergy, and mast cell activation tests (MATs). The MATs were shown to be comparably predictive to BATs, although not precisely.
Both tests involve exposing allergenic proteins to the cells in question to see if the IgE antibodies attached to them will bind with the protein and cause them to degranulate. If it does, the patient is allergic. The problem with BAT is that since the basophils circulate in the blood, the test must be done when the sample is fresh. There is no way to achieve the economies of scale enjoyed by commercial testing services that perform other kinds (and less definitive) of allergy testing. For this reason BAT has been confined to research centers.
The MAT has a singular advantage. The key is that the mast cells aren’t taken from the individual, which would involve harvesting from tissue and the same kind of time pressure as the BAT. This would be far more intrusive than drawing blood.
Instead the lab uses something called LAD2 mast cells (or FcepsilonRI+/CD117+), which can be cultured in large quantities. They are blank slates with the high-affinity receptors ready to receive IgE antibodies. The patient’s plasma, which contains allergen-specific IgE, is drawn and shipped at low temperature to the lab where it is exposed to the cultured mast cells. The IgE binds to the receptors just as they do in the human body, and then exposed to the allergen. If they degranulate, there is an allergy. If they don’t—bingo, tolerance in a test tube.
The weaknesses of current blood tests are well known. As Santos et al write, “Peanut-specific IgE (P-sIgE) is associated with false-positive results and overdiagnosis.” And component tests have their problems too. “Measurement of Ara h 2–specific IgE is more accurate but is associated with false-negative results.” Oral food challenges, with their risks of adverse reactions, are the only definitive solution, but as we have written on this website before, many allergists won’t do them for reasons that include money, staff time, and the possibility of having to manage reactions.
The authors say that apart from diagnosis, the MAT seems to have real utility for predicting severity of reactions and would be a useful screen prior to food challenge
We have also written, and the Santos team concur, that the recent proliferation of treatments, whether things like various forms of immunotherapy, traditional Chinese medicine, or LAMP vaccine demands that there be new ways of measuring tolerance. It didn’t matter as much when there were no treatments, but now there are. Submitting patients to a continual series of challenges would be impractical and anxiety producing.
If proven for peanut and for other allergens, the mast cell activation test will be a welcome addition to the allergist tool kit.