Researchers have in the past found that low levels of immunoglobulin-M antibodies correlate with an increased risk of thrombosis, the blockage of a blood vessel by, for example, fragments of a ruptured atherosclerotic plaque. Here, more details regarding this relationship are reported, suggesting that therapies designed to increase immunoglobulin-M antibody levels could be useful in reducing the incidence of heart attack and stroke resulting from thrombosis.
Antibodies are an important component of the immune system. On the one hand, these proteins serve in the body to defend against microbes, and on the other hand to remove the body's own "cell waste". Naturally occurring antibodies which are present from birth and mostly of the immunoglobulin-M (IgM) type, play an essential role in these processes. In the context of thrombosis, earlier studies demonstrated that people with a low number of IgM antibodies have an increased risk of thrombosis. Thrombotic occlusion of blood vessels, which leads to myocardial infarctions, strokes, and venous thromboembolisms, is the major cause of death in the western hemisphere. Therefore, it is of critical importance to understand mechanisms preventing thrombus formation.
Microvesicles, blebs shed from the membrane of cells, are critical mediators of blood coagulation and thrombus formation. Researchers have now demonstrated that natural IgM antibodies that bind oxidation-specific epitopes can prevent coagulation and thrombosis induced by microvesicles. This provides a mechanistic explanation for the previously published observation that low levels of these antibodies are associated with an increased risk of thrombosis. Both in experiments on a mouse model and directly on human blood samples, the scientists were able to show that the addition of IgM antibodies inhibited blood clotting caused by specific microvesicles and protected mice from lung thrombosis. Conversely, it was also shown that depletion of the IgM antibodies increased blood clotting.
"The results offer high potential for novel treatments to reduce the risk of thrombosis. Influencing IgM antibody levels in high-risk patients could be a viable addition to the previously established blood thinning treatment, as this is also known to be associated with side effects such as an increased tendency to bleed in the case of injuries."