Peptide Microarray Epitope Mapping for Food Allergy Prognosis
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Solution Overview
Problem
Current diagnostic modalities for food allergy, such as skin prick testing and serum specific IgE levels, fail to provide prognostic information on whether an individual will outgrow their allergy, and methods using IgE epitopes alone are not sufficient for reliable prediction.
Innovation Solution
An in vitro method involving a peptide microarray-based competitive inhibition assay to determine antibody binding affinity and epitope diversity by incubating a sample with a peptide library immobilized on a solid support, using a competitor to reduce antibody binding, and quantifying the difference in binding in the presence and absence of the competitor to predict allergy persistence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If skin prick testing and serum specific IgE levels are used for food allergy diagnosis, then diagnostic indication of clinical reactivity is provided, but prognostic information and distinction between different phenotypes of food allergy are not provided
Solution Approach 1:
The patent segments the allergen into multiple overlapping peptides (e.g., 15-mer peptides with 10-mer overlap) that collectively cover the entire allergen sequence. This segmentation allows identification of specific epitope patterns recognized by patient antibodies, providing detailed prognostic information about allergy persistence or tolerance that cannot be obtained from whole allergen testing alone.
Solution Approach 2:
The patent introduces peptide microarrays as an intermediary tool between traditional IgE testing and clinical prognosis. The microarray serves as a mediator that captures antibody binding patterns across multiple epitopes, translating complex immune responses into quantifiable data about epitope diversity and binding affinity that predict clinical outcomes.
2Reliability
If IgE epitopes alone are used for prediction, then simplicity is maintained, but reliability of prediction is insufficient
Solution Approach 1:
The patent makes the peptide microarray methodology universal by applying it to multiple different food allergens (milk, egg, peanut, shellfish, fish, tree nuts). The same technical platform and analysis approach work across different allergen types, providing reliable predictions through consistent measurement of epitope diversity and binding affinity regardless of the specific allergen.
Solution Approach 2:
The patent changes the measurement parameters from simple IgE presence/absence to quantitative assessment of epitope diversity (number of different epitopes recognized) and binding affinity (strength of antibody-epitope interaction). These parameter changes significantly improve prediction reliability by capturing the nuanced characteristics of the immune response that simple IgE levels cannot detect.
3Measurement precision
If SPOTS membrane technology is used for epitope mapping, then epitope recognition patterns are identified, but time and labor intensity increase
Solution Approach 1:
The patent replaces the manual SPOTS membrane technology with an automated peptide microarray system. Instead of manually spotting peptides onto membranes and performing labor-intensive analysis, the microarray platform uses automated synthesis or spotting of peptides on a solid support, followed by automated detection and analysis, dramatically improving testing efficiency while maintaining or enhancing epitope mapping precision.
Solution Approach 2:
The patent utilizes a solid support (microarray substrate) that can be porous or have high surface area, allowing dense packing of numerous peptide sequences in a small space. This enables comprehensive epitope mapping of multiple peptides simultaneously, providing high-resolution epitope data much faster than sequential SPOTS membrane analysis.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Provides specific, reliable, and efficient methods for predicting whether a subject will outgrow a food allergy by analyzing antibody binding affinity and epitope diversity, allowing for tailored treatment approaches.
Implementation Method 1
incubating said sample with a peptide library corresponding to said allergen immobilized on a solid support, wherein said peptide library comprises a series of overlapping peptides, the peptides being fragments of the allergen, wherein the overlapping peptides comprise epitopes from the allergen
Implementation Method 2
incubating a first portion of the incubation mixture with a competitor, wherein said competitor comprises the epitopes of said allergen, and incubating a second portion of the incubation mixture under the same conditions but in the absence of said competitor
Data Source
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AI summary
The invention provides an in vitro method for diagnosing whether a subject allergic to a food is likely to outgrow the allergy by determining antibody binding affinity to the food allergen in an antibody-containing sample obtained from the subject.