World Health 10 Part Healthy Heart Series: Part II

Without a doubt, one of the most interesting developments in food chemistry and coronary pathophysiology in the first half of 2018 were the headlines on meat allergies (1). Just as few could have predicted the rise over the last few decades in anaphylaxis to nuts in so many individuals, so it is going with meat products. For a decade, an IgE mediated immune reaction to a carbohydrate moiety known as alpha-gal (galatctose-alpha-1,3-galactose), related to blood type groups in meats such as beef, lamb and pork, has been known. In 2008, a hypersensitivity reaction to the pharmacologic agent cetuximab was reported and related to the presence of an IgE antibody to alpha-gal (2). Since then, multiple reports of immediate or delayed allergic reactions to red meat have appeared (3,4). A cross reaction from the consequences of a tick bite, in this case the Lonestar tick (Amblyomma americanum) was defined. A clustering of cases in areas where ticks are prevalent, like the Southeast coast of the USA, was identified (5).  Labs have identified a novel IgE antibody response to alpha-gal with 2 distinct forms of anaphylaxis: an immediate-onset anaphylaxis and delayed onset reactions 3 to 6 hours after ingestion of meat (5,6).  The connection to the Lonestar tick has been tracked in southern, eastern, and central USA, Europe, Australia, and parts of Asia.

A possible connection to the presence and extent of coronary atherosclerosis has just been reported from the University of Virginia, a state with a dense population of ticks (7). The authors hypothesized that it was possible that specific IgE on mast cells, including those in coronary arteries, could increase the inflammatory response to dietary glycolipids. A prior study in 2006 had identified a high frequency of anti-carbohydrate antibodies in patients with advanced atherosclerosis but the possible connection to an immune response to a tick exposure cross reacting with a meat moiety was not appreciated then (8). The University of Virginia researchers therefore intravascular ultrasound imaging in a population where sensitization is prevalent to investigate whether the presence of IgE sensitization to α-Gal is related to the burden of (coronary artery disease) CAD. They studied 118 patients undergoing cardiac catheterization and intravascular ultrasound (IVUS). They also had measurements of total and specific IgE to alpha-gal as well as quantitative cardiac plaque determinations. The IgE antibody to alpha-gal from meat was found in a stunning 26% of the cardiac patients.  Atheroma burden as quantified on IVUS was higher in patients sensitized to alpha-gal. The association was stronger in patients <65 years of age who might be expected to have lesser burdens of atheroma. The plaques in patients with IgE to alpha-gal had more unstable features. To evaluate if this was a finding related to alpha-gal or more random, the strength of the association was assessed for total IgE and specifically alpha-gal IgE but the relationship was strongest for the alpha-gal IgE.  Even after for adjustment for standard predictors of coronary atherosclerosis, the sensitization to meat remained a significant predictor of plaque burden.  The researchers indicated that “a link between a food allergen and CAD may not seem a priori obvious, but there are several elements of the immune response to α-Gal that argue for biological plausibility. Because many, or perhaps most, subjects with IgE to α-Gal do not have allergic symptoms, an implication is that many people, despite mounting a unique and potentially detrimental immune response to α-Gal, continue to consume foods that contain the oligosaccharide allergen”.

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