Background: We have previously defined IgE+ as the IgE on basophils from a subset of highly allergic asthmatic subjects that release histamine after stimulation with histamine-releasing factor (HRF). The mechanism of IgE+ remains an enigma. Recently, there have been reports of monomeric highly cytokinergic IgEs causing mediator release, cytokine release, and phosphorylation events in cultured rodent and human mast cells in the absence of antigen.
Objective: We investigated whether human IgE+ might exist as highly cytokinergic IgE in the human system.
Methods: IgE+ was defined as causing greater than 10% histamine release by using HRF as a stimulus of human basophils. By definition, IgE- did not support histamine release to HRF. Once defined, serum and various purified human IgEs were used to stimulate purified human basophils or cultured human mast cells. The cells were examined for histamine release, extracellular signal-regulated kinase (ERK) phosphorylation, and IL-13 secretion.
Results: We found that neither IgE+ nor IgE- induced ERK phosphorylation, histamine release, and IL-13 release from freshly isolated basophils in the absence of a specific antigen. However, human IgE alone did stimulate ERK phosphorylation in cultured human mast cells and IL-3-primed human basophils.
Conclusion: Human IgE+ is not an equivalent of the mouse highly cytokinergic IgE. However, human IgE did have effects on cultured mast cells and basophils. The effect of highly cytokinergic IgE on ERK phosphorylation and cytokine secretion might be due to the priming effect of human basophils and mast cells.