Presence of IgE Autoantibodies Against Eosinophil Peroxidase and Eosinophil Cationic Protein in Severe Chronic Spontaneous Urticaria and Atopic Dermatitis

Abstract

Purpose Eosinophils are frequently found in atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) that release eosinophil peroxidase (EPX) and eosinophil cationic protein (ECP). Continuous exposure to these proteins could trigger an autoimmune response which may contribute to the pathogenesis and severity of skin inflammation. In this study, we investigate the immunoglobulin E (IgE) response against eosinophil proteins in CSU and AD. Methods We recruited patients with severe AD, severe CSU and healthy subjects to explore the presence of IgE autoantibodies and cross-reactivity against EPX, ECP and thyroid peroxidase (TPO). The potential cross-reactive epitopes among the peroxidase family were determined using in silico tools. Results The frequencies of anti-EPX IgE (28.8%) and anti-ECP IgE (26.6%) were higher in the AD group, and anti-TPO IgE was higher in the CSU group (27.2%). In the CSU group, there was a correlation between the anti-EPX IgE and anti-TPO IgE levels ( r = 0.542, P < 0.001); TPO inhibited 42% of IgE binding to EPX, while EPX inhibited 59% of IgE binding to TPO, suggesting a cross-reactivity with EPX as a primary sensitizer. There was greater inhibition when we used a pool of sera CSU and AD, TPO inhibited 52% of IgE binding to EPX, while EPX inhibited 78% of IgE binding to TPO. In silico analysis showed a possible shared epitope in the peroxidase protein family. Conclusions IgE against eosinophil proteins may contribute to chronic inflammation in patients with AD and CSU. Cross-reactivity between EPX and TPO could explain thyroid problems in CSU patients.

Urticaria

“…Furthermore, evidence in support of IgE autoantibodies as a driver of CSU includes high rates of positive skin prick tests with TPO in patients with CSU with increased levels of IgE anti-TPO and successful experiments of passive transfer of IgE anti-TPO 88 . Cross-reactivity between proteins, for example between TPO (not present in the skin) and EPO (present in the skin) 89 , and expression of autoallergens in the skin, for example IL-24, might explain why IgE-autoallergen interaction leads to activation of mast cells in skin rather than in other organs 90 .…”

IgG Autoantibodies Against IgE from Atopic Dermatitis Can Induce the Release of Cytokines and Proinflammatory Mediators from Basophils and Mast Cells

“…These controversial findings do not necessarily rule out the ability of some of these autoantibodies to activate human tissue mast cells. In any instance, the recent documentation of IgE autoantibodies against eosinophil peroxidase and eosinophil cationic protein in some patients with CSU and AD further reinforce the notion that shared, dysregulated immune functions may differentially contribute to the pathogenesis of these conditions ( 55 ).…”

Potential contribution of Helicobacter pylori proteins in the pathogenesis of type 1 gastric neuroendocrine tumor and urticaria. In silico approach

“…Its quality was evaluated by several tools, including the Ramachandran graphs, WHATIF, QMEAN4 index and energy values (GROMOS96 force field). All models were visualized with Pymol 2.3 [ 16 , 17 ].…”

“…pylori antigens. Only epitopes with a score above of 0,7 and more than 4 residues were selected [ 16 , 17 ].…”