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Cardiovascular disease is a major cause of illness in the population as a whole. Recently, it has come to be seen in relation to immune reactions in which autoantibodies (antibodies directed against structures within the individual’s own body) are formed. These autoantibodies are now thought to be an important cause of severe cardiovascular disease. Antibodies, which are proteins, are normally directed against external substances (e.g. viruses or bacteria), rendering them harmless. Over the last few years, teams at the Institute for Immunology and Transfusion Medicine (Immunohematology) and Internal Medicine Clinic B (Cardiology) at Ernst Moritz Arndt University in Greifswald have pooled their internationally acclaimed research activities. They are now working together on joint projects relating to autoimmune responses in patients with cardiovascular disease. The researchers have been able to show that organ-specific autoantibodies play central roles both in the immune reaction against blood cells that can be induced in the blood by biologics (e.g. heparin) and in the heart muscle weakness typical of dilated cardiomyopathy (DCM).

Focusing upon heparin-induced thrombocytopenia as an example, the research teams recently succeeded in applying methods from biophysics and nanotechnology to characterize the highly complex structure of the antigens leading to antibody formation. With the aid of these methods, they were able to demonstrate the presence of immune complexes in biological systems and to measure and produce images of these complexes using Atomic Force Microscopy (AFM).

 

 

Figure (left): Image of PF-4 molecules; Figure (right): Image of immune complexes (PF-4 and heparin) in patients with HIT (heparin induced thrombocytopenia) after administration of heparin

 

These high resolution imaging techniques will come to play an increasingly important role in our research on the mechanisms and complex molecular structures of autoantibodies, supplementing the methods already used in immunohematology and cardiology. The focus of this research is upon two disorders of the cardiovascular system (HIT and DCM) which are caused by similar processes.

 

 

HIT (heparin induced thrombocytopenia)
DCM (dilated cardiomyopathy)
Underlying Mechanisms