PDGF Receptor Alpha Epitope Peptides for Autoantibody Detection
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Solution Overview
Problem
The detection of anti-PDGFR auto-antibodies in SSc patients is challenging due to technical limitations and conflicting reports, primarily because of the need for high concentrations of total class G immunoglobulins, which has led to uncertainty about the agonistic autoimmune reaction's role in SSc pathogenesis.
Innovation Solution
The development of specific peptides from the extracellular region of the human PDGF receptor alpha and the generation of recombinant human monoclonal auto-antibodies (rHu-maab) that target these peptides, allowing for the detection of auto-antibodies and understanding of SSc-specific pathogenic mechanisms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If high concentrations of total class G immunoglobulins are used for detection, then detection sensitivity is improved, but measurement precision deteriorates due to conflicting reports and technical limitations
Solution Approach 1:
The patent extracts the specific epitope region (aa 284-304) from the full PDGFR alpha extracellular domain to create a focused detection target. This extraction allows detection using smaller, more specific peptide amounts rather than requiring high concentrations of total immunoglobulins, thereby improving measurement precision while reducing the quantity of substance needed.
Solution Approach 2:
The invention applies local quality by targeting a specific local region (epitope aa 284-304) of the PDGFR alpha protein rather than using general total immunoglobulins. This localized approach enables precise detection of autoantibodies against this specific epitope, improving measurement precision without requiring high concentrations of bulk immunoglobulin preparations.
2Reliability
If recombinant human monoclonal auto-antibodies are developed, then diagnostic reliability is improved, but device complexity increases
Solution Approach 1:
The patent segments the complex task of autoantibody detection into distinct components: (1) identification of the specific epitope region (aa 284-304), (2) generation of recombinant human monoclonal auto-antibodies targeting this epitope, and (3) use of these standardized reagents for detection. This segmentation improves diagnostic reliability through standardized reagents while managing complexity by breaking down the system into modular, well-defined components.
Solution Approach 2:
The invention changes the parameter of antibody specificity by developing recombinant human monoclonal auto-antibodies that target a specific epitope (aa 284-304) rather than using polyclonal or non-specific antibodies. This parameter change improves diagnostic reliability through high specificity while the recombinant nature of these antibodies provides standardized, reproducible reagents that manage system complexity.
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
These peptides and antibodies provide a robust diagnostic and therapeutic tool for SSc, confirming the autoimmune process targeting PDGFR and elucidating the pathogenesis, enabling improved monitoring and treatment strategies.
Implementation Method 1
peptides comprised in the extracellular region of human PDGF receptor (hPDGFR) alpha... able to bind human auto-antibodies
Data Source
Figure 1a~1c
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Figure 2b
AI summary
The present invention refers to peptides comprised in the extracellular region of human PDGF receptor (hPDGFR) alpha, their use for detecting auto-antibodies anti-hPDGFR alpha and to a method for the diagnosis or the monitoring control for therapy of SSc. The present invention also refers to antibodies or recombinant or synthetic derivatives thereof able to recognize and bind to the above peptide and to their use in the treatment of SSc.