Anti-CarP Antibody Detection for Arthritis Subgroup Classification

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for diagnosing arthritis, particularly rheumatoid arthritis, are inadequate as they often result in incorrect diagnoses and fail to accurately differentiate between individuals who will spontaneously remit and those who will progress to a chronic form, due to the heterogeneity of the arthritis population and the lack of effective assays for ACPA-negative RA.

Innovation Solution

The development of a method to classify individuals based on the detection of Anti-Carbamylated Protein (Anti-CarP) antibodies in body fluids, specifically using anti-CarP IgA antibodies to predict the risk of developing RA and estimate the severity of arthritis, which can be used in conjunction with existing tests like ACPA and CCP2 tests.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current diagnostic methods (ACR/EULAR 2010 criteria, RF and ACPA tests) are used to diagnose arthritis, then diagnosis can be made with more certainty, but the heterogeneity of the arthritis population leads to incorrect diagnoses and failure to differentiate between spontaneous remission and progression to chronic RA

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidability to differentiate patient subgroups
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The invention segments the arthritis population into distinct subgroups based on antibody profiles. By detecting specific antibodies (anti-carbamylated protein IgA, ACPA, RF) and analyzing their combinations, the method divides the heterogeneous arthritis population into categories with different prognoses (spontaneous remission vs. progression to chronic RA), enabling tailored diagnostic and treatment approaches for each subgroup

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces new diagnostic parameters (anti-carbamylated protein IgA antibody levels and their combinations with ACPA and RF) to enhance the ability to differentiate patient subgroups. These additional parameters provide more granular classification capability beyond the traditional ACR/EULAR criteria, allowing better prediction of disease progression and remission patterns

Inventive Principle:
Principle #35Parameter changes

2Reliability

If screening tests for arthritis indicators (chemokines, cytokines, rheumatoid factor, ACPA) are performed, then the diagnosis can be improved, but the complexity of the testing protocol increases and may lead to wrong diagnoses in heterogeneous populations

Engineering Contradiction:
Improvediagnosis reliabilityVSAvoidtesting protocol complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention applies partial action by focusing on specific, high-value antibody combinations rather than comprehensive screening of all possible arthritis indicators. The method identifies key antibody pairs (anti-CarP IgA with ACPA and RF) that provide the most discriminatory power for prognosis, avoiding the need to test all available markers and reducing protocol complexity while maintaining high reliability

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The invention uses specific antibody combinations as intermediary markers that mediate between clinical presentation and disease outcome. These antibody profiles serve as intermediaries that translate complex immunological responses into actionable diagnostic categories, simplifying the interpretation of heterogeneous arthritis presentations while maintaining diagnostic reliability

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If only ACPA tests are used to classify arthritis patients, then ACPA positive RA can be identified, but ACPA negative RA patients cannot be properly identified or subtyped

Engineering Contradiction:
ImproveACPA positive RA detectionVSAvoididentification of ACPA negative RA
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The invention creates a universal diagnostic approach that works for both ACPA positive and ACPA negative RA patients. By using anti-carbamylated protein IgA antibodies as a core marker that can identify disease risk and progression in both ACPA positive and ACPA negative individuals, the method provides a multi-functional classification system that adapts to different patient subsets rather than being limited to ACPA detection alone

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

Data Source

PatentEP2927690B1Anti-carbamylated protein antibodies and the risk for arthritis
Publication Date: 2022.10.26 ACADEMISCH ZIEKENHUIS LEIDEN (H O D N LUMC)
  • EP2927690B1 patent drawingFigure 1A
  • EP2927690B1 patent drawingFigure 1B
  • EP2927690B1 patent drawingFigure 1C

AI summary

Antibodies against citrullinated protein antigens (ACPA) have shown their relevance for the diagnosis and possibly pathogenesis in arthritis. The present invention provides means and methods for determining antibodies against homocitrulline containing proteins or carbamylated proteins/peptides (anti-CarP) for the classification of individuals suffering from or at risk of suffering from arthritis.