Immunoglobulin E (IgE) and ischemic heart disease. Which came first, the chicken or the egg?

Several lines of evidence demonstrate that the immune system plays a pivotal role in development and progression of ischemic heart disease (IHD). More recently, a series of biological and clinical investigations has generated new interest about the existence of a relationship between a specific class of immunoglobulin, that is immunoglobulin E (IgE), and IHD. Data obtained in several epidemiological studies have convincingly demonstrated that the concentration of total serum IgEs is significantly increased in patients with IHD and often correlates with the prognosis. The putative mechanisms are essentially mediated by a physiological interaction between IgEs and mast cells, which triggers the direct or indirect release of a variety of substances that are actively involved in the pathogenesis of myocardial ischemia and thrombosis. Regardless of these important evidences, a causality dilemma remains, since it is still unclear whether increased IgE levels are a consequence of IHD or, rather, IHD is an underlying cause of increased IgE levels. The answer would allow us to recognize whether total IgEs may be considered simple biomarkers or risk factors of IHD, thus paving the way to investigations focused on immunotherapy or avoidance of allergenic foods for reducing serum IgEs in patients at risk of IHD.