What is the significance of Eosinophil-Derived Neurotoxin (EDN) and Major Basic Protein (MBP) in eosinophil activation for health?

From the Guidelines

Eosinophil-Derived Neurotoxin (EDN) and Major Basic Protein (MBP) play a crucial role in eosinophil activation, contributing to the pathogenesis of eosinophilic esophagitis (EoE) and other atopic diseases, and their significance for health lies in their potential as biomarkers for eosinophilic inflammation and targets for therapeutic intervention. The management of EoE, a chronic and rare food antigen-driven Th2 inflammatory condition of the esophagus, is complex and involves various therapeutic strategies, including topical glucocorticosteroids, dietary elimination, and esophageal dilation 1. EoE is characterized by symptoms such as dysphagia and food impaction, visual esophageal endoscopic findings, and histopathology revealing eosinophils in the esophageal epithelium, with a threshold of ≥15 eosinophils per high-power field (eos/hpf) defining the condition 1.

Key Points

• EoE is a chronic and rare condition that affects approximately 1 in every 2000 people, with a large body of evidence suggesting that EoE subjects have aeroallergen sensitization and concurrent atopic diseases, including asthma, allergic rhinitis, and eczema 1.
• The primary outcome for interventions in EoE is achieving <15 eos/hpf, except for esophageal dilation, and the most common management approaches include topical glucocorticosteroids, dietary elimination, and esophageal dilation 1.
• The significance of EDN and MBP in eosinophil activation for health lies in their potential as biomarkers for eosinophilic inflammation and targets for therapeutic intervention, highlighting the importance of controlling eosinophilic inflammation in managing EoE and other atopic diseases 1.
• Elevated levels of EDN and MBP can indicate active eosinophilic inflammation and help clinicians monitor disease activity and response to treatment, particularly in EoE management, where persistently high levels despite treatment might suggest the need for adjusting anti-inflammatory medications or considering biologics that target eosinophilic pathways 1.

Therapeutic Implications

• The management of EoE involves various therapeutic strategies, including topical glucocorticosteroids, dietary elimination, and esophageal dilation, with the goal of achieving <15 eos/hpf and improving symptoms and quality of life 1.
• The use of EDN and MBP as biomarkers for eosinophilic inflammation can help guide therapeutic decisions and monitor response to treatment, highlighting the importance of personalized medicine approaches in EoE management 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Eosinophil-Derived Neurotoxin (EDN) and Major Basic Protein (MBP) Significance

• Eosinophils play a crucial role in the development of allergic and non-allergic asthma phenotypes, with activated eosinophils being significantly associated with asthma severity 2
• Activated eosinophils release several potent toxic signaling molecules, including major basic proteins, eosinophil peroxidase, eosinophil cationic protein (ECP), and lipid mediators, which can render tissue damage and lead to allergic manifestations 2
• Eosinophil-derived neurotoxin (EDN) and major basic protein (MBP) are among the granule proteins released by eosinophils, which can contribute to tissue damage and inflammation 3
• The release of EDN and MBP by eosinophils can be influenced by various factors, including interleukin-5 (IL-5) and other pro-inflammatory cytokines 4, 3

Eosinophil Activation and Health

• Eosinophil activation is strictly associated with the activation of other hetero-cellular populations, such as neutrophils, macrophages, mast cells, and platelets, which can culminate in the onset and progression of abnormal phenotypes, including bronchoconstriction, allergic response, fibrosis, and oxidative stress 2
• Eosinophil activation can lead to the release of various tissue-destructive proinflammatory mediators and cytotoxic proteins, which can be both beneficial and detrimental to the host 3
• The regulation of eosinophil activation and the release of EDN and MBP are critical in maintaining tissue homeostasis and preventing excessive inflammation and tissue damage 5, 6

Therapeutic Targeting of Eosinophils

• Targeting eosinophil apoptosis is a potential therapeutic strategy for the treatment of allergic asthma, with various anti-asthmatic agents, such as glucocorticoids and anti-IL-5 antibodies, promoting eosinophil apoptosis 4
• Therapeutic strategies for harnessing human eosinophils in allergic inflammation, hypereosinophilic disorders, and cancer are being explored, including the targeting of IL-5 and IL-5R, and the potential for harnessing eosinophil cytotoxicity as a tumoricide 3