Eosinophil-derived neurotoxin: A biologically and analytically attractive asthma biomarker

Abstract

There is a growing body of evidence for the utility of eosinophil-derived neurotoxin (EDN) as a biomarker in asthma, including association with eosinophilic airway inflammation, assessment of disease severity and potential for predicting pathogenic risks, including exacerbations. However, to interpret any biomarker data with confidence, it is first important to understand the preanalytical factors and biological variation that may affect its reliable measurement and results interpretation. In this study we defined the healthy serum EDN reference range for men and women as 1.98 to 26.10 ng/mL, with no significant gender differences. Smoking did not impact the mean EDN levels and no circadian rhythm was identified for EDN, unlike blood eosinophils (EOS) where levels peaked at 00:00h. EDN expression in different cell types was investigated and shown to occur primarily in eosinophils, indicating they are likely to be the main cellular repository for EDN. We also confirm that the quantification of serum EDN is not influenced by the type of storage tube used, and it is stable at ambient temperature or when refrigerated for at least 7 days and for up to one year when frozen at -20°C or -80°C. In summary, EDN is a stable biomarker that may prove useful in precision medicine approaches by enabling the identification of a subpopulation of asthma patients with activated eosinophils and a more severe form of the disease.

Longitudinal eosinophil‐derived neurotoxin measurements and asthma development in preschool wheezers

“…Eosinophils are involved in the innate and adaptive immune systems and play an essential role in asthma and allergic diseases. Eosinophil‐derived neurotoxin (EDN), one of the major proteins in eosinophilic granules, has antiviral and antibacterial activity, and its release is triggered by pro‐inflammatory mediators 3,4 . Available information about EDN as a biomarker for asthma diagnosis is limited.…”

“…Idun Holmdahl 1,2 Angela Hoyer 1,2 Helena Ekoff 3 Anders Sjölander 3 Niclas Rydell 3 Gunilla Hedlin 1,2 Jon R. Konradsen 1,2 Cilla Söderhäll…”

Asthma and Allergy: Unravelling a Tangled Relationship with a Focus on New Biomarkers and Treatment

“…Finally, from a clinical standpoint, the finding that EDN levels can be measured in multiple specimen types, such as sputum, serum, urine, bronchoalveolar lavage fluid, and nasal lavage fluid [ 88 , 89 , 90 , 91 , 92 ] and, in contrast to BEC, are less affected by circadian rhythm or gender differences [ 93 ] expand its potential usefulness in routine practice. Table 2 illustrates the relative pros and cos of available Type 2 asthma biomarkers.…”

Metabolomics, Microbiota, and In Vivo and In Vitro Biomarkers in Type 2 Severe Asthma: A Perspective Review

“…In serum, it has been observed an increase in ECP levels among asthmatics compared to healthy non-smoking subjects, but other respiratory diseases such as chronic obstructive pulmonary disease (COPD), interstitial lung diseases, acute respiratory infections, eosinophilic granulomatosis with polyangiitis (EGPA), chronic eosinophilic pneumonia and allergic rhinitis may be associated with a similar increase. On the other side, ECP levels have been reported to decrease in response to treatment with the anti-IL-5Ra drug benralizumab [38]. To date, ECP has shown prognostic properties associated with increased risk of exacerbations and uncontrolled asthma; however, its predictive properties are still limited, principally due to overlap with many other pulmonary disorders.…”

“…The study of microbiota has revolutionized the understanding of human diseases. Indeed, the advent of metagenomics techniques has revealed the presence of microorganisms in sites that were previously considered sterile, such as the lower respiratory tract (LRT) [38]. The microbiota of the respiratory tract consists of bacteria, fungi, and viruses.…”