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US-12618827-B2 - Compositions and methods for individualized characterization of non-IgE mediated food allergies

US12618827B2US 12618827 B2US12618827 B2US 12618827B2US-12618827-B2

Abstract

Provided herein are compositions and methods for the individualized identification of triggers allergies (e.g., non-IgE mediated allergies) in an individual. In particular, biomarkers and assays are provided and used to characterize food allergies and related conditions (e.g., food protein-induced enterocolitis syndrome (FPIES), eosinophilic esophagitis (EoE), etc.) in an individual, by identifying safe and trigger foods without the need for oral challenge.

Inventors

  • Mohamad El Zaatari
  • John Y. Kao

Assignees

  • THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Dates

Publication Date
20260505
Application Date
20200717

Claims (10)

  1. 1 . A method comprising: (a) growing cells from a subject that suffers from a non-IgE mediated allergic sensitivity in growth media in contact with a food item; (b) detecting the expression level of a panel of 1000 or fewer biomarkers in the cells, the panel of biomarkers comprising TNFSF15, SPP1, MMP19, IL6,-CCL20, CCL3, CXCL2, CCL3L3, and SPINK1; (c) comparing the expression level of the biomarkers to threshold and/or control levels of expression for the biomarkers; (d) determining that the food item is a safe substance because the expression level of the biomarkers is beneath the threshold and/or control levels of expression; and (e) administering the food item to the subject.
  2. 2 . The method of claim 1 , wherein a food item that is not a safe substance will cause non-IgE mediated allergies in the subject.
  3. 3 . The method of claim 1 , wherein the subject suffers from food protein-induced enterocolitis syndrome (FPIES).
  4. 4 . The method of claim 1 , wherein the subject suffers from eosinophilic esophagitis (EoE).
  5. 5 . The method of claim 1 , further comprising a step of liquifying or homogenizing the food item before adding the food item to the growth media as a liquid or homogenized sample.
  6. 6 . The method of claim 1 , wherein the expression level comprises the RNA expression level.
  7. 7 . The method of claim 1 , wherein the expression level comprises the protein expression level.
  8. 8 . The method of claim 1 , wherein the panel further comprises one or more biomarkers selected from INHBA, F3, TM4SF19, CSF2, FNIP2, GEM, CSF1, EMP1, ZC3H12C, SERPINB2, OR10D3, CCRL2, PPARG, ATF3, IL2A, SOCS3, and TNF.
  9. 9 . The method of claim 1 , wherein the cells are white blood cells.
  10. 10 . The method of claim 1 , wherein the cells are dissociated esophageal cells from mucosal biopsy.

Description

FIELD Provided herein are compositions and methods for the individualized identification of triggers allergies (e.g., non-IgE mediated allergies) in an individual. In particular, biomarkers and assays are provided and used to characterize food allergies and related conditions (e.g., a food protein-induced enterocolitis syndrome (FPIES), eosinophilic esophagitis (EoE), etc.) in an individual, by identifying safe and trigger foods without the need for oral challenge. BACKGROUND Food protein-induced enterocolitis syndrome (FPIES) is a debilitating disorder in which infants and toddlers react to a wide variety of foods. The disorder usually leads to the child's inability to eat the majority of foods, with the most severe cases allowing for 0-2 tolerated foods only. The reaction to food is severe and comprises profuse vomiting (4-20 times per reaction), with the risk of hypovolemic shock. This reaction is mediated by the immune system, and is delayed, occurring 2-6 hours after trigger food ingestion. Even though FPIES usually resolves on its own at ages 3-5 years, the malnutrition and food aversion that develop during this period often lead to failure to thrive in infants and toddlers and may require a nasogastric feeding tube, or total parenteral nutrition (TPN). Based on the severity of FPIES, there is dire need to develop alternative strategies for the management of this disease. Eosinophilic esophagitis (EoE) is an allergic swallowing disorder. EoE affects the esophagus, the part of the gastrointestinal tract (gut) that connects the back of the throat to the stomach. EoE occurs when eosinophils collect in the esophagus, and it is often triggered by food. EoE occurs in both children and adults. There is no clinical test to identify “safe” versus “trigger” foods for non-IgE mediated allergies (e.g., FPIES, EoE, etc.). For example, for patients with FPIES, typically infants and toddlers, the parents are directed to trial different foods in what is termed oral food challenges (OFCs) to be able to identify safe versus trigger foods. In other words, the parents are directed to randomly trial one food ingredient at a time (repetitively for 5 to 7 days) to identify safe versus trigger foods. In EoE, patients are directed to follow a 4-food elimination diet, and then undergo endoscopy to assess esophageal inflammation. Each of the 4 foods is then re-introduced one a time, and the patients are scoped repeatedly to identify the “safe” versus “trigger” foods. These processes are usually dangerous/painful for the subjects, difficult on parents/patients, and time consuming. Instead of these OFCs and random food challenges, what is needed is a test that accurately identifies “safe” versus “trigger” foods without subjecting the subject to challenges or elimination diets. SUMMARY Provided herein are compositions and methods for the individualized identification of safe foods and triggers of non-IgE mediated allergies in an individual. In particular, biomarkers and assays are provided and used to characterize a food protein-induced enterocolitis syndrome (FPIES) in an individual, by identifying safe and trigger foods without the need for oral challenge. Provided herein are tests that can provide a substitute for food challenges and elimination diets. The tests are performed in culture and circumvents subjugating subjects (e.g., infants and toddlers) to adverse allergic reactions. In some embodiments, peripheral white blood cells or other cells (e.g., dissociated esophageal biopsy cells) from the patient are treated with various test foods. Gene expression of the cells is then analyzed (e.g., by RT-qPCR) to identify the presence/level of various biomarkers of non-IgE mediated allergies. These biomarkers accurately predict safe (non-trigger) foods. In some embodiments, provided herein are biomarkers that are indicative of non IgE-mediated allergies (e.g., FPIES, EoE, etc.). In some embodiments, biomarkers are selected from TNFSF15, INHBA, SPP1, F3, MMP19, IL6, CCL20, TM4SF19, CSF2, CCL3, CXCL2, FNIP2, GEM, CCL3L3, CSF1, EMP1, ZC3H12C, SERPINB2, OR10D3, SPINK1, CCRL2, PPARG, ATF3, IL1A, SOCS3, and TNF. In some embodiments, biomarkers are selected from TNFSF15, SPP1, SPINK1, IL-6, CCL3L3, MMP19, CCL20, CCL3, and CXCL2. In some embodiments, provided herein are methods of assessing the allergic sensitivity of a subject to an item comprising: (a) growing cells from the subject in growth media in contact with the item; (b) detecting the expression level in the cells of one or more biomarkers of allergic sensitivity; (c) comparing the expression level of the one or more biomarkers to threshold and/or control levels of expression; and (d) determining whether the item is a safe substance or trigger substance. In some embodiments, provided herein are methods of assessing the allergic sensitivity of a subject to an item comprising: (a) growing cells from the subject in growth media in contact with the item; (b) detecting the expression le