Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency.

Rationale: Deficiency of secreted IgM (sIgM ^-/- ) accelerates atherosclerosis in Ldlr ^-/- mice. Several atheroprotective effects of increased levels of IgM antibodies have been suggested, including preventing inflammation induced by oxidized low-density lipoprotein and promoting apoptotic cell clearance. However, the mechanisms by which the lack of sIgM promotes lesion formation remain unknown.
Objective: To identify the mechanisms by which sIgM deficiency accelerates atherosclerosis in mice.
Methods and Results: We here show that both sIgM ^-/- and Ldlr ^-/- sIgM ^-/- mice develop increased plasma IgE titers because of impaired generation of B cells expressing the low-affinity IgE receptor CD23, which mediates the clearance of IgE antibodies. We further report that Ldlr ^-/- sIgM ^-/- mice exhibit increased numbers of activated mast cells and neutrophils in the perivascular area of atherosclerotic plaques. Treatment with an anti-IgE-neutralizing antibody fully reversed vascular inflammation and accelerated atherosclerotic lesion formation in cholesterol-fed Ldlr ^-/- sIgM ^-/- mice.
Conclusions: Thus, our data identify a previously unsuspected mechanism by which sIgM deficiency aggravates atherosclerosis.
(© 2016 American Heart Association, Inc.)