Cardiovascular diseases are among the most common causes of death worldwide. The question of whether and to what extent the immune system influences the development of cardiovascular diseases is increasingly coming into focus. One relatively new finding, for example, is that autoantibodies, i.e. antibodies against the body's own structures, appear to play an important role.
To find out more about this, a team from Preventive Cardiology and Preventive Medicine and Clinical Epidemiology and Systems Medicine at Mainz University Medical Center led by Dr. Felix Müller and research group leader Prof. Dr. Philipp Wild examined around 5,000 participants. This took place as part of the Gutenberg Health Study (GHS) - a large-scale representative population study in the Rhine-Main region, Germany. The investigations focused on autoantibodies directed against the so-called chemokine receptor 3 (CXCR3). CXCR3 is a protein receptor that is found in particular on the surface of immune cells. It therefore serves as a biomarker for the development of inflammatory diseases and could therefore be a suitable target structure for the development of new drugs.
"We have found that people with cardiovascular diseases, such as atrial fibrillation or atherosclerosis, have a higher concentration of these autoantibodies. This is associated with pathological changes in the heart muscle and arteries. We had already methodically excluded people suffering from an autoimmune disease or cancer or taking medication that impairs the immune system from the study. Surprisingly, measurable concentrations of autoantibodies against CXCR3 were nevertheless found in almost all study participants," explains Professor Wild.
Another exciting finding: the concentration of autoantibodies also allowed a prediction to be made in healthy study participants as to whether they might suffer from a disease in the future and whether there is an increased risk of death. The prognosis using the autoantibodies was independent of all established risk factors for cardiovascular diseases such as obesity, diabetes and high blood pressure.
The research team at the UKSH, Lübeck Campus, and the University of Lübeck led by Prof Dr Gabriela Riemekasten, Director of the Clinic for Rheumatology and Clinical Immunology, has been conducting basic research into autoantibodies in autoimmune diseases for a long time. Interestingly, the researchers had also found measurable concentrations of these autoantibodies in healthy control subjects. This gave rise to the idea of conducting a population sample in collaboration with the Mainz scientists in order to investigate the relevance of autoantibodies for the general population. Further experimental data from the Lübeck Institute of Cardiogenetics and the Department of Rheumatology and Clinical Immunology confirmed the findings from the GHS.
"In our study, we found clear evidence that antibodies against CXCR3 play a major role in the formation of atherosclerotic plaques, i.e. vascular changes caused by inflammation, in the arteries. The more autoantibodies were detectable, the higher the risk of developing cardiovascular disease. We were also able to prove this in a mouse model for atherosclerosis, i.e. vascular calcification. This discovery is remarkable because it shows how autoimmune reactions can influence heart health," says Professor Riemekasten.
As part of the study, the scientists collaborated with the company CellTrend GmbH (Luckenwalde). CellTrend was the first company to develop a diagnostic for the detection of antibodies against CXCR3, provided its test for the investigations and carried out the determination of CXCR3 antibodies as part of the project. Founded in 1998, the company specialises in the detection of antibodies against G protein-coupled receptors (GPCR).
The results published in the European Heart Journal are now being further analysed for their potential for the development of new therapies as part of the BMBF future cluster "curATime". The aim of curATime is to develop RNA-based drugs for the treatment of cardiovascular diseases.
Original publication: Autoantibodies against the chemokine receptor 3 predict cardiovascular risk (F.S. Müller et al., 2023)
Scientific contact:
Prof. Dr. Philipp Wild, Preventive Cardiology and Medical Prevention, Clinical Epidemiology and Systems Medicine, Mainz University Medical Center,
Telephone: 06131 17-7163, e-mail: philipp.wild@unimedizin-mainz.de
Prof. D.r Gabriela Riemekasten, Clinic for Rheumatology and Clinical Immunology, University Medical Centre Schleswig-Holstein, Campus Lübeck,
Phone: 0451 500-45206, e-mail: gabriela.riemekasten@uksh.de
Source: Press release University Medical Centre Mainz (in German only)
