I recently received a request to explain the differences between the Mediator Release Test (MRT) and the Cyrex food sensitivity panel. I’ve asked Board Certified Naturopath Diana C. Bright, MS, RD, CCN, CLT, CGP to lay it out all for us. Here is how Dr. Bright explains it:
To understand immunology I had to read “How the Immune System Works” 2nd Edition by Lauren Sompayrac for my ND Program. I believe he simplifies this complex topic. I highly recommend this book. He says immunology is a difficult subject to study for several reasons. First, there are lots of details, and sometimes these details get in the way of understanding the concepts. Second difficulty in learning immunology is that there is an exception to every rule. He begins by creating a big picture describing what the innate and adaptive immune systems are. Since I have been studying this for some time, I hope this makes sense in understanding Cyrex 4 and MRT. I have included my comments in parenthesis:
Since Cyrex tests for IgG, confusion arises because we have learned that IgG is an unreliable test as a diagnostic tool for food-induced hypersensitivity.
There are subclasses of IgG and the study referred to regarding this conclusion is on IgG4 by Stapel, et al (1). Staple, et al, concluded food-specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components.
According to Sampayrac (2) subclasses of IgG have different functions. In an interview with Dr. Vojdani from Cyrex in 2014 with Dr. Tom O’Bryan from the Gluten Summit, he admitted he was the one who developed the IgG testing by ELISA in 1985, but discovered it was not correct. He says based on how our immune system is built, the first line of defense becomes activated and makes IgA antibodies against any component of that food. They are secreted in the saliva and mucosal areas which are part of the innate immune system. Then overflow gets into the blood and the adaptive immune system is triggered to make antibodies against the enemy. Dr. Vojdani also said, “With delayed reactions, you don’t know which arm of the armed forces (immune system) is called upon.” Dr. Vojdani further pointed out that IgG and IgM are more responsible when the food antigens get into circulation.
So how does Cyrex 4 compare to MRT?
MRT is an ‘end-point’ test. Dr. Mark Pasula says it is not concerned about the immunological pathway (the various armed forces of the immune system) although it involves a variety of immune mechanisms (IgG, IgM, IgA, C3, C4, T-cell activation, phagocytosis, etc.) and non-immune mechanisms (pharmacologic, toxic) working independently or concurrently to trigger inflammatory and neurological mediators released from associated leukocytes and platelets. (It covers all the pathways or arms of the immune system, innate and adaptive.)
He further says, “Neutrophils and monocytes/macrophages are first responders in innate pathways. Other cells, such as tissue mast cells, eosinophils, and lymphocytes, are involved in reactions related to both adaptive and innate pathways. Whether reactions are governed by innate or adaptive pathways, mediator release from white cells are the immunological “end point” of all food-induced inflammatory reactions.”
MRT measures a volume displacement of mediators released into the blood involving detection of Lymphocytes, Monocytes, Neutrophils and Eosinophils that are triggered to release mediators. Dr. Pasula says, “The released mediators produce corresponding physiologic effects leading to symptom manifestation.” Hence, MRT quantifies the response of the immune system to each antigen (chemicals and foods).
For further detailed explanation of the MRT test, refer to Dr. Mark J. Pasula’s, PhD, paper “The Patented Mediator Release Test (MRT): A Comprehensive Blood Test for Inflammation Caused by Food and Food-Chemical Sensitivities, Townsend Letter – January 2014.
MRT’s Sensitivity is 94.5%, Specificity 91.7% and Split Sample Reproducibility is >90%. I don’t know of any other test that matches that accuracy in this industry. No test is 100%, but MRT comes close. The primary conditions we support, IBS-D, Migraines and Fibromyalgia, are Type IV Hypersensitivities, which are cell-mediated, not involving antibodies. Dr. Pasula says, “It is worth noting that the most commonly ordered blood test to help identify culprit food items – food-specific IgG – is a response of the adaptive immune system, as is type 4 delayed-type hypersensitivity governed by sensitized T cells (lymphocyte transformation).”
Regarding Cyrex Array 4 Test (Gluten-Associated Cross-Reactive Foods and Food Sensitivity–24 foods), IgG and IgM are measured. It is said that when the body is overwhelmed with reactive foods, such as foods containing gluten, IgA can’t be produced enough, so IgG and then IgM come into play. I am told foods must be eaten for antibodies to be produced for this test. When a food is reactive, IgA will step to the plate first, building up. When it can’t keep up with the reactive foods, then IgG, then IgM come into play. (Sampayrac says IgM antibodies is the default antibody class. IgG antibodies are the longest lived antibody class, with a half life of about three weeks and IgM antibodies have a half life of only about one day. I am guessing this is why Cyrex only tests for IgG rather than IgM.)
Array 4 is specifically for those individuals who have been on a GF diet for about a year and are not doing well because of possible cross reactivity of gluten with other foods. Twenty-four foods are tested.
Viewing the “end-point” of inflammatory reaction rather than isolating the individual actors involved gives us a more complete and holistic view of how that person’s body will react to that substance. For this reason, it is inescapable to conclude that the antibody tests offered by Cyrex are not as clinically useful as the results from the MRT.
I am ever more convinced that the MRT is the gold standard in food sensitivity testing and when followed by the LEAP dietary therapy program, it is the best path to removing inflammation and feeling better.
(1) Allergy. 2008 Jul;63(7):793-6. Epub 2008 May 16. Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report. Stapel SO, Asero R, Ballmer-Weber BK, Knol EF, Strobel S, Vieths S, Kleine-Tebbe J; EAACI Task Force. Sanquin Diagnostic Services, Amsterdam, the Netherlands).
(2) Sompayrac, How the Immune System Works, 2nd Edition 2003, p. 35.