Autoantibody Detection Panel Using Gluk Polypeptides

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Solution Overview

Problem

Current diagnostic methods for neurological autoimmune diseases, particularly those associated with autoantibodies to Gluk1, Gluk2, Gluk3, Gluk4, and Gluk5, face challenges in specificity, sensitivity, and early detection, leading to potential misdiagnosis or delayed treatment, as many patients do not have detectable antibodies with state-of-the-art tests and lack specific clinical patterns.

Innovation Solution

A method involving the detection of autoantibodies binding specifically to Gluk1, Gluk2, Gluk3, Gluk4, and Gluk5 using a diagnostically useful carrier with immobilized polypeptides, combined with additional antigens, to enhance diagnostic reliability through specific antibody-antigen interactions and detection techniques such as ELISA or immunofluorescence.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If state-of-the-art tests are used to detect autoantibodies, then diagnostic reliability is improved, but many patients still have undetectable antibodies leading to misdiagnosis

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddiagnostic accuracy
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention segments the diagnostic approach by dividing the panel into multiple groups of antigens (e.g., Group 1: NMDAR, LGI1, GABA_B; Group 2: AMPAR, GluK1-5; Group 3: CASPR2, DPPX). This segmentation allows systematic detection across different antibody targets, ensuring that patients with antibodies against any specific antigen group can be identified, thereby resolving the contradiction between detection sensitivity and diagnostic accuracy.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention creates a universal diagnostic panel that can detect multiple types of autoantibodies simultaneously across diverse neurological conditions. The multi-antigen panel serves multiple functions: detecting antibodies against NMDAR, AMPAR, GluK receptors, and other targets in a single assay, thereby improving both detection sensitivity and diagnostic accuracy across various autoimmune encephalitis cases.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Reliability

If a comprehensive panel of antigens is used to improve detection coverage, then diagnostic reliability is improved, but device complexity and cost increase

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

Solution Approach 1:

The comprehensive antigen panel is segmented into manageable groups (Group 1, Group 2, Group 3, etc.), each containing specific antigens that can be detected together. This segmentation reduces assay complexity by allowing modular implementation while maintaining comprehensive coverage for diagnostic accuracy.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention merges multiple antigen detection capabilities into a single integrated panel assay. By combining detection of antibodies against NMDAR, AMPAR, GluK1-5, LGI1, GABA_B, CASPR2, and other antigens in one test, it achieves comprehensive diagnostic accuracy while streamlining the overall testing process compared to multiple separate assays.

Inventive Principle:
Principle #5Merging (Combining)

3Loss of time

If specific clinical patterns are absent, then differential diagnosis becomes difficult, but early treatment is needed to prevent irreversible damage

Engineering Contradiction:
Improvetime to diagnosisVSAvoiddiagnostic confidence
Core Design Contradiction:
Loss of timeVSReliability

Solution Approach 1:

The invention enables preliminary diagnostic action by providing a comprehensive antibody detection panel that can identify autoimmune encephalitis before specific clinical patterns fully develop. The panel detects antibodies against multiple antigens (NMDAR, AMPAR, GluK1-5, LGI1, etc.), allowing early intervention to prevent irreversible neurological damage even when clinical presentation is atypical or evolving.

Inventive Principle:
Principle #10Preliminary action

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 improves the specificity and sensitivity of diagnosing neurological autoimmune diseases and cancers by accurately identifying autoantibodies, aiding in early detection and differentiation from other conditions, thereby facilitating timely and appropriate treatment.

Implementation Method 1

detecting in a sample an autoantibody binding specifically to one or more from the group comprising Gluk1, Gluk2, Gluk3, Gluk4, and Gluk5

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentUS20240255502A9Method and reagents for the detection of an autoantibody
Publication Date: 2024.08.01 INSTITUCIO CATALANA DE RECERCA I ESTUDIS AVANCATS (ICREA)
  • US20240255502A9 patent drawing
  • US20240255502A9 patent drawing
  • US20240255502A9 patent drawing

AI summary

A method involves detecting in a sample an autoantibody binding specifically to one or more from Gluk1, Gluk2, Gluk3, Gluk4 and Gluk5, preferably Gluk2. An autoantibody binds specifically to one or more from Gluk1, Gluk2, Gluk3, Gluk4 and Gluk5, preferably Gluk2. A diagnostically useful carrier with a solid phase with an immobilized polypeptide contains one or more from Gluk1, Gluk2, Gluk3, Gluk4 and Gluk5, preferably Gluk2 or a variant thereof. The autoantibody can be used for diagnosing a neurological autoimmune disease or a cancer.