DNER Protein-Based Assay for Anti-Tr Antibody Detection

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Solution Overview

Problem

The diagnosis of Hodgkin lymphoma-associated paraneoplastic cerebellar degeneration (PCD) is hindered by the lack of an identified antigen for anti-Tr antibodies, relying on indirect methods that are less reliable than antigen-based detection.

Innovation Solution

Identification of the DNER protein as the antigen capable of binding to anti-Tr antibodies, enabling a direct and reliable method for detecting these antibodies through immunoassays, including cell-based assays using labeled DNER protein or antigenic parts thereof.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If indirect methods (immunohistochemistry with blocking experiments) are used to detect anti-Tr antibodies, then diagnosis can be performed without identified antigen, but diagnostic reliability and precision are reduced

Engineering Contradiction:
Improvediagnostic reliabilityVSAvoidassay complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and identifies the specific antigen (DNER protein) recognized by anti-Tr antibodies from the complex immunological system. This extraction of the key antigen component enables direct detection methods, resolving the contradiction by providing a reliable diagnostic tool without requiring complex indirect blocking experiments.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent creates a cell-based assay system that expresses the DNER antigen, serving as a simplified model that replicates the antigen-antibody interaction. This copied system allows direct detection of anti-Tr antibodies in patient samples, improving reliability while maintaining operational simplicity compared to complex blocking experiments.

Inventive Principle:
Principle #26Copying

2Measurement precision

If antigen blocking experiments are performed to confirm anti-Tr antibody presence, then diagnostic accuracy improves, but time consumption and procedural complexity increase

Engineering Contradiction:
Improvediagnostic accuracyVSAvoiddiagnostic time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary identification and characterization of the DNER antigen before clinical testing. By having the antigen identified and validated in advance, the actual diagnostic process can proceed directly with antibody detection using the known antigen, eliminating the need for time-consuming blocking experiments during patient diagnosis.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent develops a cell-based assay that copies the essential antigen-antibody interaction in a simplified, standardized format. This copied system allows rapid direct detection of anti-Tr antibodies without requiring complex blocking procedures, thereby improving measurement precision while reducing diagnostic time.

Inventive Principle:
Principle #26Copying

3Measurement precision

If indirect immunohistochemical methods are used for anti-Tr antibody detection, then antigen identification is avoided, but measurement precision and diagnostic reliability deteriorate

Engineering Contradiction:
Improveantibody detection precisionVSAvoidassay implementation ease
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent extracts the specific DNER antigen from the complex system and characterizes it fully. This extraction enables the development of direct detection assays with high measurement precision, while the standardized cell-based expression system maintains ease of implementation by avoiding the need for complex tissue preparation and blocking procedures.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent creates a simplified cell-based model that copies the essential antigen-antibody interaction. This copied system achieves high measurement precision through direct detection while maintaining ease of manufacture through standardized cell culture and assay procedures, eliminating the complexity of indirect immunohistochemical methods.

Inventive Principle:
Principle #26Copying

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

This approach simplifies the detection of anti-Tr antibodies, providing a quick and reliable assay for diagnosing Hodgkin lymphoma-associated PCD, improving diagnostic accuracy and efficiency.

Implementation Method 1

testing the presence of said antibodies in said sample by addition of DNER protein or an antigenic part thereof and checking whether said DNER protein is bound by any antibodies in said sample

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentUS9097716B2Assay for anti-TR antibodies
Publication Date: 2015.08.04 ERASMUS UNIV MEDICAL CENT ROTTERDAM ERASMUS MC
  • US9097716B2 patent drawing
  • US9097716B2 patent drawing
  • US9097716B2 patent drawing

AI summary

The present invention relates to a method for determining the presence of anti-Tr antibodies in a subject comprising the steps of obtaining a sample from said subject testing the presence of said antibodies in said sample by addition of DNER protein or an antigenic part thereof and checking whether said DNER protein is bound by any antibodies in said sample Such an assay is useful for the diagnosis of paraneoplastic cerebellar degeneration that is associated with Hodgkin lymphoma, or, more generally, to type patients suffering from cerebellar ataxia. Also comprised in the invention is a kit for performing such an assay.