Complement Receptor Immobilization for Pathogen Removal
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Solution Overview
Problem
The widespread use of antibiotics has led to the development of drug-resistant pathogens, particularly in hospital and care facility settings, where drug-resistant infections pose a significant threat due to compromised immune systems and high prevalence of resistant bacteria.
Innovation Solution
The use of complement receptors, such as CRIg, immobilized on high surface area polymers or in dialysate, to opsonize pathogens in biological fluids, facilitating their removal through extracorporeal devices, thereby enhancing the body's immune response and reducing the spread of infections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibiotics are used to treat infections, then bacterial growth is inhibited, but drug-resistant pathogens develop
Solution Approach 1:
Complement receptors (CR1, CR2, CR3, CR4, CRIg) serve as intermediary molecules that bind to opsonized pathogens and facilitate their removal by phagocytes. This alternative mechanism bypasses antibiotic resistance by using the body's innate immune system rather than chemical antibiotics.
Solution Approach 2:
The invention leverages the body's own immune system components (complement proteins and phagocytes) to fight infections. By enhancing rather than replacing natural immune mechanisms, the treatment maintains effectiveness against drug-resistant pathogens without contributing to further resistance development.
2Productivity
If complement receptors are introduced to enhance pathogen removal, then pathogen clearance is improved, but excessive complement activation may cause adverse effects
Solution Approach 1:
The invention modifies the concentration and distribution parameters of complement receptors. By immobilizing receptors on extracorporeal devices rather than systemically administering them, the local concentration at the treatment site is high while systemic exposure is minimized, improving pathogen removal while reducing adverse effects.
Solution Approach 2:
Complement inhibitors act as intermediary molecules that modulate the complement system's activity. They prevent excessive activation and tissue damage while allowing sufficient complement-mediated pathogen opsonization and clearance to occur.
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 effectively filters out opsonized pathogens from biological fluids, including blood, reducing the severity and spread of drug-resistant infections by leveraging the body's immune system, while minimizing adverse effects from excessive complement activation.
Implementation Method 1
When pathogens are opsonized with complement proteins including components of C3 such as iC3b (alternatively spelled C3bi), they can be detected by various receptors including, for example, CR1, CR3, CR4, and CRIg.
Implementation Method 2
The phagocytes then ingest the tagged pathogens (via phagocytosis) allowing the immune system to remove the tagged pathogens.
Implementation Method 3
The present disclosure provides methods and systems for treating a biological fluid of a subject suffering from a microbial infection. In some embodiments, these methods and systems involve a complement receptor immobilized on, or otherwise associated with a polymer substrate
Data Source
AI summary
The present disclosure provides methods and systems for treating a biological fluid of a subject suffering from a microbial infection (e.g., a drug-resistant microbial infection). In some embodiments, these methods and systems involve a complement receptor immobilized on, or otherwise associated with a polymer substrate, for example, high surface area particles, membranes, hollow fibers, and/or other porous or non-porous media. In other embodiments, the methods and systems involve a complement receptor present in a dialysate used in a dialyzer for extracting pathogens out of a biological fluid, for example, the blood of a patient.