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Immunomodulation and autoimmunity in cardiovascular disease and atherosclerosis


Atherosclerosis, the major cause of cardiovascular disease (CVD) is an inflammatory disease, where the immune system plays an important role. Novel autoantibodies as protection or risk markers and therapy through immunomodulation could be a major advance in prevention and treatment of CVD. One example is natural antibodies against phosphorylcholine (aPC), an antigen exposed in some bacteria and in phospholipids with platelet activating factor (PAF)-activity, e g in oxidized LDL. Our clinical and experimental studies indicate that aPC, mainly of IgM type protect against atherosclerosis and CVD. Risk markers are thrombogenic antiphospholipid antibodies (aPL), and our main focus is novel types of aPL against platelet activating factor (PAF) or PAF-like lipids (aPAF). In a prototypic autoimmune disease, SLE, such aPL are raised and the risk of CVD is very high. Closely associated with these markers are our novel therapeutic principles. One is to raise the levels of aPC, through passive immunization, with polyclonal aPC from pooled human Ig, or with monoclonal aPC. Active immunization with PC is a later possibility. Decreased binding of antithrombotic Annexin V to endothelium is associated with CVD in SLE and potentially in some infectious diseases. Neutralizing antibodies in pooled human Ig restores Annexin V binding and these are thus a therapeutic possibility. Annexin V per se could also prevent CVD.
The CVDIMMUNE combines academic and industrial expertise and objectives, and aims at:
-Investigating novel risk markers for CVD in European patient cohorts of in about 15 000 patients including unique cohorts as the Swedish Twin registry, the MORGAM-study and SLE.
-Investigating immunomodulation as a therapeutic strategy for of CVD.
-Developing documentation for registration of diagnostic ELISA kits in EU and the US.
-Developing proof of concept for at least one pharmaceutical product candidate.
-Providing a strong research foundation and knowledge on mechanisms.

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Karolinska Institutet
Contribution de l’UE
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Nobels väg 5

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Participants (10)