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Antibodies against Phosphorylcholine-Implications for Chronic Inflammatory Diseases
1IMM, Nobels Väg 13, Karolinska Institutet, 17165 Stockholm, Sweden.
Insights
Elevated antibodies against phosphorylcholine (PC) are linked to protection against chronic inflammatory diseases like atherosclerosis and cardiovascular disease (CVD). Immunization strategies targeting PC may offer therapeutic benefits.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Inflammation Research
Background:
- Atherosclerosis and cardiovascular disease (CVD) are leading causes of death globally, recognized as chronic inflammatory conditions.
- Chronic inflammation underlies various diseases, including autoimmune disorders like systemic lupus erythematosus (SLE), diabetes, obesity, and osteoarthritis.
- Systemic lupus erythematosus (SLE) is associated with increased atherosclerosis and a high risk of CVD, highlighting the immune system's role.
Purpose of the Study:
- To investigate the role of antibodies against phosphorylcholine (PC) in chronic inflammatory conditions, particularly atherosclerosis and CVD.
- To explore the potential of modulating anti-PC antibody levels for therapeutic interventions in chronic inflammation.
Main Methods:
- Review of existing literature on phosphorylcholine (PC) as a molecular pattern (DAMP/PAMP).
- Analysis of the association between anti-PC antibodies (IgM and IgG1) and protection in chronic inflammatory diseases.
- Examination of animal experimental data involving immunization to raise anti-PC levels.
Main Results:
- Phosphorylcholine (PC) acts as both a danger-associated molecular pattern (DAMP) and a pathogen-associated molecular pattern (PAMP).
- Ubiquitous anti-PC antibodies, particularly IgM and IgG1, are associated with protection against chronic inflammatory conditions and develop post-natally.
- Animal studies demonstrate that immunization to increase anti-PC levels ameliorates atherosclerosis and other chronic inflammatory conditions.
Conclusions:
- Anti-PC antibodies may exert protective effects through anti-inflammatory and immune-modulatory mechanisms, including clearance of dead cells and pathogen defense.
- Raising anti-PC antibody levels via immunization presents a potential strategy for preventing and treating chronic inflammatory diseases like atherosclerosis and CVD.
Abstract:
Atherosclerosis and its main consequence, cardiovascular disease (CVD) are nowadays regarded as chronic inflammatory disease conditions, and CVD is the main cause of death in the world. Other examples of chronic inflammation are rheumatic and other autoimmune conditions, but also diabetes, obesity, and even osteoarthritis among others. In addition, infectious diseases can have traits in common with these conditions. Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, where atherosclerosis is increased and the risk of CVD is very high. This is a clinical problem but could also shed light on the role of the immune system in atherosclerosis and CVD. Underlying mechanisms are of major interest and these are only partially known. Phosphorylcholine (PC) is a small lipid-related antigen, which is both a danger associated molecular pattern (DAMP), and a pathogen associated molecular pattern (PAMP). Antibodies against PC are ubiquitous and 5-10% of circulating IgM is IgM anti-PC. Anti-PC, especially IgM and IgG1 anti-PC, has been associated with protection in the chronic inflammatory conditions mentioned above, and develops during the first years of life, while being present at very low levels at birth. Animal experiments with immunization to raise anti-PC ameliorate atherosclerosis and other chronic inflammatory conditions. Potential mechanisms include anti-inflammatory, immune modulatory, clearance of dead cells and protection against infectious agents. An intriguing possibility is to raise anti-PC levels through immunization, to prevent and/or ameliorate chronic inflammation.
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