Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans

2009/04/14 by Meng-Yun Chou, Linda Fogelstrand, Karsten Hartvigsen +12 · 469 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Acquired immune system #Antibody #Atherosclerosis and Cardiovascular Diseases #Biochemistry #Biology #Cell biology #Epitope #Homeostasis #Immune system #Immunology #Inflammasome and immune disorders #Inflammation #Innate immune system #Lipoprotein #Neutrophil, Myeloperoxidase and Oxidative Mechanisms #Pattern recognition receptor #Receptor #Scavenger receptor

paper · open access · doi:10.1172/jci36800

published in Journal of Clinical Investigation 119(5), 1335-1349 (American Society for Clinical Investigation)

openalex publication_date 2009/04/14 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these epitopes are also recognized by innate receptors, such as scavenger receptors on macrophages, and plasma proteins, such as C-reactive protein (CRP). Here, we provide multiple lines of evidence that oxidation-specific epitopes constitute a dominant, previously unrecognized target of natural Abs (NAbs) in both mice and humans. Using reconstituted mice expressing solely IgM NAbs, we have shown that approximately 30% of all NAbs bound to model oxidation-specific epitopes, as well as to atherosclerotic lesions and apoptotic cells. Because oxidative processes are ubiquitous, we hypothesized that these epitopes exert selective pressure to expand NAbs, which in turn play an important role in mediating homeostatic functions consequent to inflammation and cell death, as demonstrated by their ability to facilitate apoptotic cell clearance. These findings provide novel insights into the functions of NAbs in mediating host homeostasis and into their roles in health and diseases, such as chronic inflammatory diseases and atherosclerosis.

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