Is Atherosclerosis an Allergic Disease?

Interesting premise.
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That was the title of a recent commentary in Circulation Research by Christoph J. Binder, MD, PhD, and Joseph L. Witztum, MD, from the University of California, San Diego (Circ Res 2011;109:1103-04).

The two commentators were impressed by Wang et. al.'s research showing the involvement of immunoglobulin E (IgE), which plays an important role in allergic reactions, in promoting atherogenesis (J Clin Invest 2011;121:3564-3577).

IgE, in relation to allergic reactions, activates mast cells by binding to IgE's high-affinity receptor FcER1. In addition to allergic responses, mast cells participate in other inflammatory diseases, including atherosclerosis, Wang and colleagues wrote.

For their study, Wang et. al. analyzed serum IgE levels in two separate Chinese populations and found them elevated in patients with myocardial infarction and unstable angina.

Those with acute MIs had the highest levels of IgE, followed by those with unstable angina, and then those with stable angina. In other words, the circulating levels of IgE correlated with plaque instability, Wang and colleagues wrote.

In addition, the investigators found IgE and FcER1 in human atherosclerotic lesions, mostly localized in macrophage-rich areas.

Prior studies had found that people with common allergic diseases such as asthma and allergic rhinitis were more prone to develop atherosclerosis (Arch Intern Med 2005;165:2521-6), suggesting a link.

But such detailed association of IgE with atherosclerosis had not been seen before, Wang et. al. said.

And what it means is not entirely clear, Binder and Witztum wrote in their commentary.

Nevertheless, "the evidence continues to accumulate supporting an important role for immunological mechanisms in all phases of atherosclerosis," the commentators said.

There is a host of "combinatorial groupings" involving IgE and other receptors that contribute to the "pro-atherogenic activity of IgE in humans," including macrophage activation and apoptosis, Binder and Witztum said.

But they focused on the fact that elevated IgE levels typically reflect allergic-type immune responses.

"It would be of great interest to know whether the increased IgE levels were polyclonal or reflected any disease-specific antigens, such as those to oxidation-specific epitopes characterized for IgG and IgM isotypes in humans and murine models of atherosclerosis."

A problem with the current study is that the levels of IgE were low overall. Also, it is unclear whether the IgE levels were a cause or product of the heart disease.

However, the evidence of IgE in atherosclerotic lesions and in serum from patients with unstable plaque "support the notion that such 'minor' immunoglobulin molecules may participate in the activation not only of mast cells, but also other blood-borne inflammatory cells ... during the pathogenesis of human atherosclerosis," Wang and colleagues concluded.