Antibodies against phosphorylcholine and protection against atherosclerosis, cardiovascular disease and chronic inflammation

ABSTRACT

Introduction

Chronic inflammatory diseases include cardiovascular disease (CVD), atherosclerosis, rheumatic and autoimmune diseases, and others, constituting a large part of the disease burden. It is therefore of major importance to improve understanding of underlying mechanisms, prediction, and treatment.

Areas covered

Broad fields including atherosclerosis, immunology, and inflammation are covered, through searches on PubMed and background knowledge. Phosphorylcholine (PC) is both a danger-associated molecular pattern (DAMP), present on oxidized LDL (OxLDL) in atherosclerotic lesions and dead cells, and a pathogen associated molecular pattern (PAMP), present on microorganisms. IgM and IgG1 antibodies against PC (anti-PC) are associated with protection in several chronic inflammatory conditions, especially in CVD and atherosclerosis where most research has been done. PC-immunization ameliorates atherosclerosis in animal models and several potential underlying mechanisms have been proposed, including anti-inflammatory, decreased uptake of OxLDL in the artery wall, promotion of T regulatory cells. Anti-PC develops during the first years of life. Low levels of IgM and IgG1 anti-PC may be caused by lack of exposure to microorganisms, including nematodes and helminths among others.

Expert opinion

anti-PC could improve prediction of clinical outcome and raising anti-PC could be developed into a novel therapy.

KEYWORDS:

• Antibodies
• atherosclerosis
• immunity
• inflammation
• phosphorylcholine

Article highlights

• Chronic inflammation including atherosclerosis and its consequence cardiovascular disease are major health problems in the world

• Phosphorylcholine (PC) is an antigen on dead cells, oxidized lipids and some pathogens

• Antibodies against PC (anti-PC) are abundant and associated with protection against the mentioned disease conditions

• Underlying mechanisms include anti-inflammatory and increased clearance of dead cells

• Raising anti-PC levels through immunization could therefore be developed as a novel therapy

Declaration of interest

J Frostegard is in the board of directors at Annexin Pharmaceuticals and is named as inventor in patents related to Annexin A5. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by grants from The Swedish Heart Lung Foundation, European Union (Intricare, Preciseads), the Swedish association against Rheumatism, King Gustav V:s 80-year fund.