Histamine-releasing factor (HRF) in asthma and atopic dermatitis (177.16)

Abstract Effects of monomeric IgE on mast cell biology exhibit vast heterogeneity, depending on IgE used. Highly cytokinergic (HC) IgEs can induce many activation events such as degranulation, cytokine production, etc, whereas poorly cytokinergic (PC) IgEs can induce only weak survival promotion. Because of the reminiscence to the heterogeneity in the ability of IgE molecules to prime basophils in response to HRF, this dichotomy has led us to find that a subset of IgEs bind to HRF via their Fab portions; the IgE-binding sites were mapped to two different sites of HRF, indicating that dimeric HRF can cross-link IgE-bound FcϵRI; N19 and H3 peptides blocked HRF-Ig interactions; administration of these inhibitors drastically reduced airway inflammation in asthma models, implying that blockade of HRF-Ig interactions may represent a potential prophylactic and therapeutic strategy for the treatment of asthma. Importantly, most HC, but no PC, IgEs exhibit polyreactivity to HRF and other autoantigens. Interestingly, sera from atopic dermatitis (AD) patients showed increased reactivity to autoantigens and increased levels of HRF. Some AD patients, but not healthy individuals, had high serum levels of HRF-reactive IgE. AD sera with high titers of autoreactive IgE could induce increased IL-8 secretion from human mast cells. Collectively, these results show support the autoimmune mechanism in the pathogenesis of atopic dermatitis.