Immunology and Chronic Disease – Johan Frostegård's research group

We study how different types of lipids, mainly phospholipids, activate immune reactions and how these affect atherosclerosis, cardiovascular disease and inflammation in general. Our translational research is both experimental and clinically oriented.

Our research focuses om protective role and mechanisms of the natural, innate antibodies against oxidation-related epitopes on phospholipids; such as phosphorylcholine (PC) and others. To identify effects of antibodies is a major challenge. Antibodies can both protect and damage and it is a balancing act to use the right antibodies in the right quantity and in the right context. Such antibodies may have prognostic and diagnostic significance, where low levels signify an increased risk of cardiovascular disease. Novel immunomodulatory therapies using protective natural antibodies can be potentially useful.

Overall aims

Our overall aims are to:

• improve risk assessment for cardiovascular disease and thereby optimize treatment
• study the causes of the inflammation linked to atherosclerosis/atherothrombosis
• develop new immunological treatments conteracting unwanted inflammation

Projects led by Johan Frostegård

Natural antibodies

A recent discovery is that antibodies against lipid antigens, especially phosphorylcholine (anti-PC) share genetic background with chronic lymphatic leukemia (CLL) and are protection markers for CLL. Ongoing collaboration with Twin Registry and also Monica Studies in Umeå will now include also CLL and some common cancer types.

Financing

• to be applied for
• Swedish Heart Lung Foundation (on general anti-PC properties

Natural antibodies against lipid antigens as phosphorylcholine (PC) and malondialdehyde (MDA)

Our group discovered novel protection markers in cardiovascular disease, including anti-PC and anti-MDA, especially IgMs. This concept is now explored in larger cohorts, in SLE prospectively.

Financing

• The Swedish Heart and Lung Foundation
• The Swedish Rheumatic Foundation
• Gustav V 80 year fund, EU (IMI)

Explorative research to identify novel therapies

We have discovered two potential therapies against Cardiovascular disease, both targeting lipid epitopes (and not peptide/protein epitopes) namely Annexin A5 and natural antibodies, anti-PC and anti-MDA. These are now in different stages of clinical development, and one is tested in patients. Hopefully we can develop a concept of vaccine against cardiovascular and inflammatory diseases.

Financing

• EU grants
• Swedish Heart Lung foundation
• RMR
• Gustav V 80årsfond

Risk markers, outcome and underlying mechanisms in SLE.

Through the SLEVIC cohort (JF is PI) we combine a unique cohort with patients from southern Stockholm (Huddinge area) with matched controls (age, sex and population). This cohort (SLEVIC) has now been followed up after 6 years, with detailed vascular and clinical measurements. We have discovered that natural lipid antibodies, especially against phosphorylcholine and malondialdehyde (anti-PC and anti-MDA) are strong protection markers, and have identified underlying mechanisms by which they may be directly involved in the disease.

Financing

• The Swedish Rheumatic Foundation
• Gustav V 80 year fund
• EU (IMI)

Risk markers, outcome and underlying mechaninsms in RA

Through collaborations, especially with Ingiäld Hafström, we study RA in large cohorts of high quality such as Barfot. We have identified anti-PC as a potential mechanism and marker for being non-responsive to biologics. Antibodies against other lipid moieties are also studied.

Financing

• The Swedish Rheumatic Foundation
• Gustav V 80 year fund
• EU (IMI)

Explorative research to identify novel therapies

We have discovered two potential therapies against Inflammatory disease (where cardiovascular diseases actually are including. These are both targeting lipid epitopes (and not peptide/protein epitopes) namely Annexin A5 and natural antibodies, anti-PC and anti-MDA which are tested clinically in cardiovascular disease but also hopefully apply to inflammatory diseases as SLE and RA which will be investigated. Also a vaccine against these lipids can hopefully be studied further.

Financing

• The Swedish Hear and Lung Foundation
• The Swedish Rheumatic Foundation
• Gustav V 80 year fund
• EU (IMI)

Risk markers, outcome and potential mechanisms and treatment in COPD.

Through a study, AHLDI, we perform at Emergency Medicine in Huddinge, we study various risk markers including novel ones as anti-PC and anti-MDA to identify outcomes, risk and potential mechanisms in acute medical diseases including chronic Fobstructive pulmonary disease.

Financing

• Swedish Heart Lung foundation