CD2 identifies a monocyte subpopulation with immunoglobulin E-dependent, high-level expression of Fc?RI

Background—FcɛRI expression by monocytes can affect monocyte function via multiple mechanisms, thereby potentially influencing the generation of allergic inflammation. Previous studies on the in vivo regulation of monocyte FcɛRI expression by ambient IgE have yielded conflicting results. Objective—We hypothesized that monocyte FcɛRI expression is limited to a specific monocyte subset and that within that subset FcɛRI surface expression is correlated to serum IgE. Methods—Study 1: Blood was obtained from nonallergic subjects (n = 14) and subjects with allergic asthma (n = 18), hypereosinophilic syndrome (n = 2), hyper-IgE syndrome (n = 6), and helminth infection (n = 4). Study 2: Blood was obtained from allergic subjects in a clinical trial of omalizumab before and during study drug treatment. Monocyte surface FcɛRI expression was measured using flow cytometry. Results—FcɛRI expression was significantly greater in the CD2 high vs. CD2 low monocyte subsets (31% vs. 1.9% median FcɛRI + , respectively). In asthmatic and non-atopic healthy control subjects, CD2 low monocytes expressed little or undetectable FcɛRI. In study 1, FcɛRI expression was highly correlated to serum IgE in the CD2 high , but not in the CD2 low monocyte subpopulation (R values of 0.67 and 0.41, respectively). In study 2, omalizumab but not placebo, caused a significant and sustained drop in FcɛRI expression within the CD2 high monocyte subset. Conclusions—CD2 defines a monocyte subset with high FcɛRI expression, the magnitude of which is highly correlated to serum IgE. As such, this new description of CD2 high monocytes as FcɛRI bearing cells suggests that they may be potential targets of anti-IgE immunomodulatory therapies.