Urine eosinophil-derived neurotoxin: A potential marker of activity in select eosinophilic disorders

Michelle A. Makiya, Paneez Khoury, Fei Li Kuang, Alexis Dominique Mata, Sana Mahmood, Abbie Bowman, David Espinoza, Nicholas Kovacs, Thomas Brown, Nicole Holland, Lauren Wetzler, Jean Anne M. Ware, Anne Marie Dyer, Praveen Akuthota, Bruce S. Bochner, Vernon M. Chinchilli, Gerald J. Gleich, Carol Langford, Peter A. Merkel, Ulrich SpecksPeter F. Weller, Michael E. Wechsler, Calman Prussin, Michael P. Fay, Amy D. Klion

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Biomarkers of eosinophilic disease activity, especially in the context of novel therapies that reduce blood eosinophil counts, are an unmet need. Absolute eosinophil count (AEC) does not accurately reflect tissue eosinophilia or eosinophil activation. Therefore, the aims of this study were to compare the reliability of plasma and urine eosinophil major basic protein 1, eosinophil cationic protein, eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase measurement and to evaluate the usefulness of eosinophil granule protein (EGP) measurement for the assessment of disease activity in patients with eosinophil-associated diseases treated with mepolizumab, benralizumab, or dexpramipexole. Methods: Eosinophil granule protein concentrations were measured in serum, plasma, and urine from healthy volunteers and patients with hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic asthma using a multiplex assay. Results: Urine EGP concentrations remained stable, whereas serum and plasma EGP concentrations increased significantly with delayed processing. Plasma (p) EDN, but not urine (u) EDN, concentration correlated with AEC and negatively correlated with prednisone dose. Both pEDN and uEDN decreased significantly following treatment of HES patients with benralizumab and EGPA patients with mepolizumab. uEDN appeared to increase with clinical relapse in both patient groups. Conclusions: Measurement of EGP in urine is noninvasive and unaffected by cellular lysis. Although plasma and urine EDN concentrations showed a similar pattern following benralizumab and mepolizumab treatment, the lack of correlation between AEC or prednisone dose and uEDN concentrations suggests that measurement of uEDN may provide a potential biomarker of disease activity in patients with HES and EGPA.

Original languageEnglish (US)
Pages (from-to)258-269
Number of pages12
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume78
Issue number1
DOIs
StatePublished - Jan 2023

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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