CAAP Peptide Panel for Sepsis Diagnosis via LC/MS

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Solution Overview

Problem

Current diagnostic markers for sepsis lack specificity and sensitivity, failing to reliably differentiate infectious-induced from non-infectious-induced systemic inflammation, which is crucial for early diagnosis and risk stratification, particularly in polytraumatized patients without underlying infection.

Innovation Solution

A mass-spectrometry based method for detecting specific peptides formed by protease-mediated proteolysis, using a panel of C-terminal peptides of alpha-1-antitrypsin (CAAPs) as clinical diagnostic markers, enabling the differentiation of infectious-induced from non-infectious-induced systemic inflammation through multiplex multiple reaction monitoring (MRM) scanning.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current diagnostic markers (CRP, PCT, interleukins) are used for sepsis diagnosis, then the diagnosis can be performed, but the sensitivity and specificity are insufficient to reliably differentiate infectious-induced from non-infectious-induced systemic inflammation

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidspecificity and sensitivity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent segments the diagnostic approach by identifying and measuring specific proteolytic cleavage products (CAAPs) of alpha-1-antitrypsin rather than using whole protein markers. This segmentation allows detection of specific inflammatory pathways activated in sepsis, improving the ability to differentiate infectious from non-infectious inflammation with higher sensitivity and specificity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses CAAPs as intermediary markers that reflect protease activity in the inflammatory response. These cleavage products serve as mediators between the infectious stimulus and the diagnostic measurement, providing more specific information about the nature of inflammation compared to traditional markers like CRP or PCT.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Loss of time

If traditional biomarker panels are used, then diagnosis can be performed, but early diagnosis and risk stratification are compromised due to lack of specificity

Engineering Contradiction:
Improveearly diagnosis timingVSAvoiddiagnostic specificity
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent enables preliminary action by detecting CAAPs at very early stages of sepsis development, before traditional markers show significant changes. The proteolytic cleavage of alpha-1-antitrypsin occurs early in the inflammatory cascade, allowing for earlier diagnosis and intervention while maintaining high diagnostic specificity through the use of specific peptide fragment measurement.

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

The method provides sensitive and specific detection of sepsis and its early stages by correlating CAAP levels with infectious-induced systemic inflammation, improving diagnostic accuracy and enabling timely clinical intervention.

Implementation Method 1

detecting specific peptides formed by protease-mediated proteolysis

Methodology Applied
Scientific EffectProtease-mediated proteolysis: Enzyme

Implementation Method 2

A mass-spectrometry based method for detecting specific peptides

Methodology Applied
Scientific EffectMass spectrometry:

Implementation Method 3

multiplex multiple reaction monitoring (MRM) scanning

Methodology Applied
Scientific EffectChromatographic separation: Chromatography

Data Source

PatentEP4224163A1Diagnosis of sepsis and systemic inflammatory response syndrome by quantitative LC/ms method
Publication Date: 2023.08.09 UNIVSKLINIKUM JENA
  • EP4224163A1 patent drawingFigure 1
  • EP4224163A1 patent drawingFigure 2
  • EP4224163A1 patent drawingFigure 3

AI summary

The invention relates to a method for quantitatively measuring a concentration of a peptide panel in a biological matrix by mass spectrometry detection, wherein multiplex multiple reaction monitoring (MRM) scanning is applied.