Enheten för immunologi och kronisk sjukdom – Johan Frostegård

Hjärt-kärlsjukdomar är den vanligaste dödsorsaken i västvärlden. De orsakas i huvudsak av åderförkalkning (ateroskleros) som är en kronisk inflammatorisk process. Vi studerar hur olika sorters fetter, främst fosfolipider, kan aktivera immunreaktioner, samt hur dessa påverkar ateroskleros, hjärt-kärl-sjukdom och inflammation i övrigt. Vår translationella forskning är såväl experimentell som kliniskt orienterad.

Åderförkalkning (ateroskleros) är en kronisk inflammatorisk process. Fetter lagras in i blodkärlsväggen och bildar så kallade aterosklerotiska plack. Inflammationen kan leda till att placken så småningom brister. Det kan då bildas en blodpropp, trombos, som stoppar upp blodflödet och infarkten eller stroken är ett faktum.

Forskargruppen har visat att naturliga, medfödda antikroppar mot ett ämne som uttrycks på fosfolipider (phosphorylkolin-PC), kan ha en skyddande effekt mot åderförkalkning och följdsjukdomar som hjärtinfarkt och stroke. Dessa antikroppar kan även ha diagnostisk betydelse, där låga nivåer medför ökad sjukdomsrisk. Att kartlägga antikroppars effekter är en stor utmaning. Antikroppar kan både skydda och skada och det är därför en balansgång att använda rätt antikroppar i rätt mängd och i rätt sammanhang.

Målsättning

Vårt mål är att genom fortsatta studier:

  • förbättra riskbedömningen vid hjärt-kärlsjukdom och därmed optimera behandlingen
  • klarlägga orsaken till den inflammation som är kopplad till åderförkalkning och kronisk inflammation
  • utveckla nya immunologiska behandlingsalternativ mot inflammationen

Projekt

Projekt 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

  • Swedish Heart Lung Foundation 

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 80 year fund

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 Heart 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

Contact

Project Mizanur Rahman 

Mechanisms of immune activation and inflammation in atherosclerosis

Mechanisms of immune activation and ensuing inflammation in human atherosclerosis is essential for improving treatment and understanding of this disease condition. We study antigens in oxidized LDL with focus on epitopes generated during lipid oxidation, including MDA and PC, also heat shock proteins, and inhibitors we discovered, as anti-MDA and anti-PC and Annexin A5 are further studied. Novel factors include statins and PCSK9-inhibition.

Financing

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

Contact

Profile image

Mizanur Rahman

Anknuten till Forskning

Projects Marta Alarcón

Genetic mechanisms and gene-environment interaction

Large international studies in SLE and other rheumatic cohorts are studied, also SLEVIC is included. Objectives include to identify underlying mechanisms of these diseases, where SLE is an important focus, and to contribute to reclassification of Rheumatic diseases.

Financing

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

Contact

Marta Alarcón

Senior Forskare

Publikationer

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Medarbetare och kontakt

Gruppledare

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Besöksadress

Institutet för miljömedicin / Institute of Environmental Medicine at Karolinska Institutet, Nobels väg 13, Stockholm, 17177, Sweden

Postadress

Institutet för miljömedicin / Institute of Environmental Medicine, Box 210, Stockholm, 17177, Sweden