Basophil Activation Test—A New Gold Standard?

By Dr. Paul Ehrlich

Again and again since we started this website, we have returned to the subject of tests that will answer once and for all whether a patient is properly allergic to a food or not. As I wrote a couple of months ago, every test is just a test, short of an oral food challenge (OFC), and double-blind, placebo-controlled food challenge (DBPCFC). A history of reacting to a food is a food challenge before the fact. Specific IgE (RAST) just shows that the immune system has been sensitized to an allergen. Skin prick tests (SPTs) show whether the patient is reactive or not and is slightly more sensitive than the RAST. Component tests show whether he is sensitive to one or more proteins that are associated with the most severe reactions. But only a controlled exposure to increasing amounts of a food will indicate a worrisome allergy or let the patient off the hook. Patients and parents wish there were some way of finding out without the risks of ingestion. What if there were a test that could be done from a blood sample where the reaction or non-reaction could take place in a test tube?

It turns out that something called the basophil activation test (BAT) someday may fill that need. I wrote about this in a recent post in the context of research, but the latest issue of the Journal of Allergy and Clinical Immunology (JACI) has two articles that discuss it as a possible part of the diagnostic repertoire short of the anxiety-provoking OFC. The principal study is “Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children” by
Alexandra F. Santos, and others, including Gideon Lack. The second is a related editorial by Drs. Sarita U. Patil and Wayne G. Shreffler.

For those who don’t know, the basophil is an effector cell that discharges a toxic soup when it encounters a perceived threat in the form of an allergen. Unlike its accomplice, the mast cell, which lodges in tissue like skin and the mucosa of the airway and digestive system, the basophil circulates in the blood, where it provides reinforcement to an allergy attack already underway. That is why it is to blame for late-phase, or biphasic reactions.

The fact that it does circulate is what makes it accessible. It can be exposed to an allergen outside the body where, according to Patil and Shreffler, “the detection of surface protein expression changes caused by allergen-induced activation that are measured by using flow cytometry.” Doing this with mast cells would be a lot harder because the tissue would have to be obtained with a biopsy.

BAT has apparently been studied for diagnosis of pollen allergies, venom allergy, and oral allergy syndrome. The new study had 43 subjects already diagnosed with peanut allergy, 36 who were peanut sensitized but were tolerant, and 25 who weren’t peanut sensitized and were peanut tolerant. The researchers retrospectively reviewed a battery of skin prick tests (SPTs), specific IgE tests to peanut and Ara h 2 component tests, and subject blood to BATs to peanut antigen. A team of three pediatric allergists examined the results for the conventional tests and predicted whether they were allergic or not. The BATs outperformed the allergists—fully 97% predictive, which is very good indeed. A subsequent experiment with an additional 65 patients also bore out these results.

If you have doubts about your child’s allergy, this does sound like good news. But there’s a long way to go. Keep in mind that most allergists in private practice won’t even do an OFC because of the time, money, and risk of adverse events.

The BAT also faces roadblocks. Patil and Shreffler point out some of the challenges: “Although the whole-blood BAT has allowed greater ease of using the test, challenges remain. Test results should be processed soon after the blood draw, and reliable results are best obtained in experienced hands. Also, the interpretation of a positive BAT result is labor intensive and not standardized. The absence of standardized flow cytometric analysis and testing outcomes still limits this testing from being applied in a more high-throughput fashion. Finally, the significant frequency of nonresponder (also referred to as nonreleaser) basophils (10% to 15%) and our lack of understanding of this phenotype has traditionally plagued use of the BAT.”

With all these unresolved issues, no wonder the ALPCO web page for the Flow CAST® Basophil Activation Test (BAT) says,
Regulatory Status:Research Use Only. Not for Use in Diagnostic Procedures.

The “new gold standard” is a long way from clinical fruition.

Basophil by chantellelafittebiol3500.blogspot.com