Research Studies on Non-IgE Allergy

We recently took my son to be involved in a research study at the PCRCD.  

Dr.Jyonouchi runs this clinic and her current research is: Th cell polarization and candida reactivity in autistic children with food allergy. It is described: "Our previous study has shown that a high percentage of ASD children with GI symptoms reveal evidence of non IgE mediated, delayed type food allergy (NFA) against common dietary proteins (DPs) and their clinical features are similar to those in non-ASD children with NFA.  In infants, the gut immune system is immature and oral tolerance develops slowly during the first 2-3 years of life.  Thus, most non-ASD/NFA children outgrow this condition by 3-4 years of age.  However, ASD/NFA children appear to require a longer time to outgrow NFA, indicating a possibility that ASD/NFA children have immune abnormalities rendering them more reactive to ‘harmless’ luminal antigens (food and commensal flora.)  In this study, we thus hypothesize that dysregulated gut mucosal immune homeostasis is associated with altered innate immune responses that affects development of T-helper (Th) subsets.  There are two specific aims for the current study:  (1) Assessment of Th cell polarization in ASD children with NFA by intracellular staining of lineage-specific cytokines in Th cells.  (2) Assessment of anti-inflammatory Th cell responses in ASD children with NFA by measuring production of counter-regulatory cytokines in response to specific luminal Ag

in comparison with responses to stimuli of innate immunity.  Our long-term objective is to assess immune abnormalities associated with oral tolerance in ASD/NFA children. Obtained data are expected to be helpful for identifying risk factors for development of NFA and dysbiosis in autistic children."

(PI: Harumi Jyonouchi, M.D.  University of Medicine and Dentistry of New Jersey-New Jersey Medical School.)

Our son, and the other FPIES children that are going there are among her "control" group.   The Non-IgE Food Allergy children without ASD (autism spectrum disorder).  

Dr.Jyonouchi has done a few studies of this nature.  In the study, she tests for the production of proinflammatory (TNF-a, IFN-g, IL-5, IL-12) and counter-regulatory (Il-10, IL-17, TGF-b, ) cytokines production to milk (whey and casein), soy, wheat (gliadin), as well as Candida.   The results can help determine classic, chronic, aytpical FPIES responses to these proteins; but mostly it can help determine where in these mechanisms the "break down" is.   Does your child have too strong proinflammatory cytokine responses?  Treating every protein as foreign and launching attacks of inflammatory mediators?  Does the body respond with proinflammatory mediators only to lack sufficient counter regulatory cytokines?  Does the body produce minimal proinflammatory mediators but then over-react with counter-regulatory cytokines?   It can define more of what is happening at this cellular level.   Past research has led to the T-cell mechanism of a Non-IgE food allergy; these tests help define that- with dairy, soy, wheat proteins. 

Dr.Jyonouchi has studied the effects of Non-IgE food allergy (by immune mechanisms to food proteins as described above) with populations of Autistic Spectrum disorders, as well as Inflammatory Bowel Diseases.  She describes Non-IgE food allergy in her paper: Non-IgE Food Allergy.

Dr.Jyonouchi concludes much of her findings for treatment around gut homeostasis, and notes in this Pediatric Allergy and Immunology article that "it is crucial for gut mucousal immmune system to establish immune homeostasis that permits us to 1). cohabit with commensal flora under a mutual benefiical relationship, 2). digest huge amounts of macronutrients without provoking immune reactions (oral tolerance), and 3). maintain effective immune defense against pathogens.  This somewhat conflicting task may make the gut mucousal immune system error prone, requiring active counter-regulatory measures such as developement of regulatory T (Treg) cells.   These measures appear to develop gradually during the first few years of life and this is why infants are prone to be reactive to common dietary proteins in IgE or Non-IgE dependent manner." 

I follow her here as much of my own research leads me here as well.   While there is much of her research that we can transfer to learn more of FPIES immune responses, mechanisms, gut flora and homeostasis in our own children....but more FPIES-specific research is needed.