The OSE complotype and its clinical potential

Area of Science:

• Immunology
• Biochemistry
• Pathology

Background:

• Cellular damage and aging induce lipid peroxidation, creating reactive products like malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE).
• These products form oxidation-specific epitopes (OSEs), acting as damage-associated molecular patterns (DAMPs) that promote sterile inflammation.
• OSEs accumulate on dying cells and oxidized lipoproteins, necessitating their recognition and clearance by the innate immune system.

Purpose of the Study:

• To review mechanisms of OSE accumulation and their pathological consequences.
• To explore interactions between OSEs and innate humoral immune components, particularly complement proteins.
• To discuss the clinical relevance of OSE-recognizing complement protein variants (OSE complotype) in disease risk assessment.

Main Methods:

• Literature review focusing on OSEs, oxidative stress, and innate immunity.
• Analysis of OSE recognition by natural IgM antibodies, pentraxins, and complement factors.
• Examination of the role of complement factors like CFH and FHR proteins in OSE clearance and modulation.

Main Results:

• Natural IgM antibodies and pentraxins bind various OSEs, including oxidized phosphocholine (OxPC), 4-HNE, and MDA.
• Complement components (C1q, C3a, CFH, FHRs) bind MDA and other OSEs, modulating inflammation.
• CFH and FHR-3 interact with 2-(ω-carboxyethyl)pyrrole (CEP), and CFH mitigates 4-HNE-induced stress.

Conclusions:

• Dysregulation of innate humoral defense against OSEs contributes to oxidative stress-related diseases.
• The OSE complotype, reflecting genetic variations in OSE-recognizing complement proteins, holds potential for disease risk stratification.
• Understanding OSE-complement interactions is crucial for developing therapeutic strategies against oxidative stress-associated pathologies.